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Pineal Gland Abstracts: 2003

Note: the following is a limited selection of abstracts available at PubMed, Science Direct, and Toxnet.

Abstracts on the Pineal Gland by Year
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2005
(Jan-June)
2004
2003
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Up to 1989


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12769226&dopt=Abstract

Can J Physiol Pharmacol. 2003 Apr;81(4):342-9.

Bidirectional communication between the pineal gland and the immune system.

Skwarlo-Sonta K, Majewski P, Markowska M, Oblap R, Olszanska B.

Department of Vertebrate Physiology, Faculty of Biology, Warsaw University, Poland. kss@biol.uw.edu.pl

The pineal gland is a vertebrate neuroendocrine organ converting environmental photoperiodic information into a biochemical message (melatonin) that subsequently regulates the activity of numerous target tissues after its release into the bloodstream. A phylogenetically conserved feature is increased melatonin synthesis during darkness, even though there are differences between mammals and birds in the regulation of rhythmic pinealocyte function. Membrane-bound melatonin receptors are found in many peripheral organs, including lymphoid glands and immune cells, from which melatonin receptor genes have been characterized and cloned. The expression of melatonin receptor genes within the immune system shows species and organ specificity. The pineal gland, via the rhythmical synthesis and release of melatonin, influences the development and function of the immune system, although the postreceptor signal transduction system is poorly understood. Circulating messages produced by activated immune cells are reciprocally perceived by the pineal gland and provide feedback for the regulation of pineal function. The pineal gland and the immune system are, therefore, reciprocally linked by bidirectional communication.

PMID: 12769226 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12753069&dopt=Abstract

J Neurochem. 2003 Jun;85(5):1101-8.

Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease.

Matsubara E, Bryant-Thomas T, Pacheco Quinto J, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leone A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA.

Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.

Increased levels of a 40-42 amino-acid peptide called the amyloid beta protein (A beta) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from A beta-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of A beta, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of beta-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.

PMID: 12753069 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15266948

Indian J Physiol Pharmacol. 2003 Oct;47(4):373-86.

Neuroprotective role of melatonin in oxidative stress vulnerable brain.

Gupta YK, Gupta M, Kohli K.

Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110 029. ykg@hotmail.com

The brain is deficient in oxidative defense mechanisms and hence is at greater risk of damage mediated by reactive oxygen species (ROS) resulting in molecular and cellular dysfunction. Emerging evidence suggesting the activation of glutamate gated cation channels, may be another source of oxidative stress, leading to neuronal degeneration. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinsonism, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, epileptic seizures, and stroke. Melatonin, the pineal hormone, acts as a direct free radical scavenger and indirect antioxidant. It is suggested that the increase in neurodegenerative diseases is attributable to a decrease in the levels of melatonin with age. Melatonin has been shown to either stimulate gene expression for the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) or to increase their activity. Additionally, it neutralizes hydoxyl radical, superoxide radical, peroxyl radical, peroxynitrite anion, singlet oxygen, hydrogen peroxide, nitric oxide, and hypochlorous acid. Unlike other antioxidants, melatonin can easily cross all morphophysiological barriers, e.g., the blood brain barrier, and enters cells and subcellular compartments. Though evidence are accumulating to suggest the potential of melatonin in neurodegenerative conditions, much information needs to be generated before the drug can find place in neurology clinics.

PMID: 15266948 [PubMed - in process]

 

Document Number: NTIS/03210051
Published: 2003

Melatonin Aging and Breast Cancer.

Hill SM

Tulane Univ., New Orleans, LA. School of Medicine.

Abstract:
Final rept. 1 Jun 2000-31 May 2003.
The pineal gland, via its hormone melatonin, inhibits the proliferation of both human and animal models of breast cancer. As humans age there is the onset of disrupted sleep leading to a significant suppression in the nocturnal levels of melatonin after age 60. We have hypothesized that the decline in pineal melatonin production, with the onset of old age, is a key factor in the age-related increase in breast cancer. Using the Buffalo rat model, we have begun to characterize the melatonin rhythm in young, middle aged and old female rats. Our studies demonstrate that the nocturnal rise in both serum and pineal melatonin is significantly blunted in old rats compared to middle aged and young rats, and is blunted in middle aged rats compared to young rats. As well, uterine MT1 melatonin receptor levels are greatly diminished in old female rats (by 80%) compared to young female rats. Finally, in our studies tissue-isolated% transplanted mammary tumors grew significantly faster and were less melatonin-responsive in old rats as compared to middle and young aged rats. In addition, tumors grown in old rats showed decreased expression of ER alpha and MT1 melatonin receptor, but greatly enhanced expression of the growth factor TGF alpha.

Order Number: 16p
Product reproduced from digital image. Order this product from NTIS by: phone at 1-800-553-NTIS (U.S. customers); (703)605-6000 (other countries); fax at (703)605-6900; and email at orders@ntis.gov. NTIS is located at 5285 Port Royal Road, Springfield, VA, 22161, USA.

Note: Other available 2003 report:

Melatonin, Aging and Breast Cancer (same title, different document).
Document Number: NTIS/00550017


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14715451&dopt=Abstract

Neurotox Res. 2003;5(5):323-7.

Neuroprotection against Abeta and glutamate toxicity by melatonin: are GABA receptors involved?

Lima AC, Louzada PR, De Mello FG, Ferreira ST.

Departamento de Bioquimica Medica, Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.

The beta-amyloid peptide (Abeta) is centrally related to the pathogenesis of Alzheimer's disease (AD). Previous studies have suggested that the neurotoxicity of Abeta may be related to the overactivation of glutamatergic transmission and excitotoxicity, and that blockade of glutamate receptors prevents Abeta-induced cell death. Here, we show that melatonin, a pineal hormone, protects chick retinal neurons in culture against the neurotoxicity of Abeta and glutamate. Right-angle light scattering and thioflavin T fluorescence measurements, as well as light microscopy analysis, indicated that, under our experimental conditions, melatonin had no effect on the aggregation of Abeta. Interestingly, the neuroprotective action of melatonin against the toxicity of Abeta was significantly decreased in the presence of picrotoxin, an antagonist of GABA(A)-like receptors. By itself, picrotoxin had no effect. These results suggest that the neuroprotective effects of melatonin against Abeta neurotoxicity could be at least in part related to a decrease in the excitatory tonus, mediated by activation of GABA receptors and the resulting hyper-polarization of the neurons. Thus, selective pharmacological manipulation of neuronal excitatory/inhibitory tonus could be a potentially interesting new approach in the treatment of AD.

PMID: 14715451 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14635944&dopt=Abstract

Reprod Suppl. 2003;61:311-21.

Origin of cerebrospinal fluid melatonin and possible function in the integration of photoperiod.

Tricoire H, Moller M, Chemineau P, Malpaux B.

UMR INRA-CNRS-Universite de Tours, Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France.

Melatonin, which is synthesized at night by the pineal gland, is present in the cerebrospinal fluid (CSF), but its entry site and its role in this compartment are not known. Using several approaches, we tested the hypothesis that melatonin enters the CSF through the pineal recess, an evagination of the third ventricle. CSF melatonin concentrations are higher near the pineal gland than in the anterior part of the third ventricle, and decrease markedly (80%) after sealing off the pineal recess. Moreover, ultrastructure and permeability analyses of the pineal-CSF interface showed that melatonin could reach the CSF either via delivery in situ by protruding pinealocytes that make direct contact with the CSF or via extracellular secretion and interstitial fluid draining into the ventricular lumen. These data indicate that melatonin in the CSF probably originates from a few pinealocytes of the basal part of the pineal gland neighbouring the pineal recess. Melatonin carried to the brain by the blood appears to be able to mediate the effects of photoperiod on reproduction, but it is unclear whether melatonin in CSF may fine-tune this response both in terms of timing and amplitude. It is critical to determine which pathway, blood or CSF, allows melatonin to reach its central targets more efficiently.

PMID: 14635944 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14519495&dopt=Abstract

Brain Res Dev Brain Res. 2003 Oct 10;145(1):71-9.

Effects of gonadal steroids on pineal morphogenesis and cell differentiation of the embryonic quail studied under cell culture conditions.

Haldar C, Fukada Y, Araki M.

Pineal Research Lab., Department of Zoology, Banaras Hindu University, 221 005, Varanasi, India

Receptors for gonadal steroid hormones have been localized in the pineal glands of several vertebrate species. No studies, however, have reported on pineal morphogenesis and cell differentiation following hormonal application in vitro during avian embryonic development. Hormonal regulation of embryonic development is crucial in all vertebrate classes. Although gonadal hormones are known to affect organogenesis in avian embryos and chicks, we wanted to investigate whether gonadal steroids (testosterone and estradiol) have any effect on the morphogenesis and cell differentiation of the avian pineal gland. The steroid hormones had a stimulatory influence on pineal morphogenesis in vitro as evidenced from the radial arrangement of colony-forming cells and the subsequent formation of a follicular-like structure under dispersed-cell culture condition. Administration of testosterone in culture medium significantly promoted the numbers of cells that were positively stained for arginine vasopressin and tyrosine hydroxylase, while estradiol showed only a slight effect. Both of the two steroid hormones significantly decreased the numbers of cells positively stained for serotonin and melatonin. Melatonin released in the culture medium decreased in content within the 24 h following steroid treatment (supported by low immunoreactivity in cultured cells and low level released to the medium). These results clearly suggest active roles of gonadal steroid hormones on embryonic pineal morphogenesis and cell differentiation and its physiological activity as they do in adult animals.

PMID: 14519495 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15323203

Ann Univ Mariae Curie Sklodowska [Med]. 2003;58(2):270-5.

Morphometry of the pineal gland in overweight individuals.

Torres K, Staskiewicz GJ, Darocha T, Czarnota A, Los T, Maciejewski R.

Department of Human Anatomy, Medical University of Lublin.

While obesity is an ever increasing problem in today's world, numerous facts suggest that its side-effects continue to be underestimated. Recent studies link obesity with pineal gland hormone and melatonin. The aim of this study was to determine differences in morphological attributes of the pineal gland in normal and overweight people in terms of pineal width and volume. A lower pineal width and volume in overweight individuals stated in the study may suggest a different excretory activity of the pineal gland.

PMID: 15323203 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14558493&dopt=Abstract

Neurol Neurochir Pol. 2003 Mar-Apr;37(2):473-84.

[In Process Citation]

[Article in Polish]

Koziarski A, Skrobowska E, Zielinski G, Warczynska A, Podgorski JK.

Kliniki Neurochirurgii Centralnego Szpitala Klinicznego WAM w Warszawie.
Nine cases of tumours located in the pineal and midbrain region in adults operated on between November 1998 and July 2002 in Dept. of Neurosurgery, Central Military Hospital in Warsaw are reported. The patients (2 men and 7 women) were aged from 27 and 69 years (mean age 43.6 years). Their main initial symptoms were caused by hydrocephalus. The histopathological examination revealed anaplastic pinealoma in 2 cases, and pineocytoma, pineal cyst, mesencephalic glial cyst, protoplasmatic astrocytoma, epidermoid cyst, unclear glial scar, and papillary ependymoma in single cases. Five patients had been treated, usually elsewhere, with shunt implantation prior to the surgery. Occipito-suboccipital osteoplastic craniotomy was performed in each case and tumours were totally removed microsurgically via the infratentorial epicerebellar approach. In one case a part of the glial periaqueductal tumour was resected additionally via the fourth ventricle and aqueduct in one stage. Postoperative haematomas in the third and fourth ventricle were found in 2 cases. Main complaints after the surgery included transient diplopia. All the patients improved significantly and resumed their previous life activities. Follow-up ranged from 3 to 44 months. Three patients with pineal tumours and one with a small postoperative ependymoma recurrence were irradiated after the surgery. One patient had been irradiated prior to surgery. Very good results of the surgical treatment of tumours in this area suggest that such patients should be referred earlier to one stage surgical management, as the procedure is easier to perform and shunt implantation may be avoided.

PMID: 14558493 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14563478&dopt=Abstract

A unique central tryptophan hydroxylase isoform.

Walther DJ, Bader M.

Max Delbruck Center for Molecular Medicine (MDC), Robert-Rossle-Strasse 10, D-13092, Berlin-Buch, Germany

Serotonin (5-hydroxytryptophan, 5-HT) is a neurotransmitter synthesized in the raphe nuclei of the brain stem and involved in the central control of food intake, sleep, and mood. Accordingly, dysfunction of the serotonin system has been implicated in the pathogenesis of psychiatric diseases. At the same time, serotonin is a peripheral hormone produced mainly by enterochromaffin cells in the intestine and stored in platelets, where it is involved in vasoconstriction, haemostasis, and the control of immune responses. Moreover, serotonin is a precursor for melatonin and is therefore synthesized in high amounts in the pineal gland. Tryptophan hydroxylase (TPH) catalyzes the rate limiting step in 5-HT synthesis. Until recently, only one gene encoding TPH was described for vertebrates. By gene targeting, we functionally ablated this gene in mice. To our surprise, the resulting animals, although being deficient for serotonin in the periphery and in the pineal gland, exhibited close to normal levels of 5-HT in the brain stem. This led us to the detection of a second TPH gene in the genome of humans, mice, and rats, called TPH2. This gene is predominantly expressed in the brain stem, while the classical TPH gene, now called TPH1, is expressed in the gut, pineal gland, spleen, and thymus. These findings clarify puzzling data, which have been collected over the last decades about partially purified TPH proteins with different characteristics and justify a new concept of the serotonin system. In fact, there are two serotonin systems in vertebrates, independently regulated and with distinct functions.

PMID: 14563478 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12960030&dopt=Abstract

Endocrinology. 2003 Oct;144(10):4648-58. Epub 2003 Jul 17.

Melatonin modulates secretion of growth hormone and prolactin by trout pituitary glands and cells in culture.

Falcon J, Besseau L, Fazzari D, Attia J, Gaildrat P, Beauchaud M, Boeuf G.

Laboratoire Arago, Unite Mixte de Recherche 7628, Centre National de la Recherche Scientifique/University P et M Curie, BP 44, F-66651 Banyuls sur Mer, France. falcon@obs-banyuls.fr.

In Teleost fish, development, growth, and reproduction are influenced by the daily and seasonal variations of photoperiod and temperature. Early in vivo studies indicated the pineal gland mediates the effects of these external factors, most probably through the rhythmic production of melatonin. The present investigation was aimed at determining whether melatonin acts directly on the pituitary to control GH and prolactin (PRL) secretion in rainbow trout. We show that 2-[125I]-iodomelatonin, a melatonin analog, binds selectively to membrane preparations and tissue sections from trout pituitaries. The affinity was within the range of that found for the binding to brain microsomal preparations, but the number of binding sites was 20-fold less than in the brain. In culture, melatonin inhibited pituitary cAMP accumulation induced by forskolin, the adenyl cyclase stimulator. Forskolin also induced an increase in GH release, which was reduced in the presence of picomolar concentrations of melatonin. At higher concentrations, the effects of melatonin became stimulatory. In the absence of forskolin, melatonin induced a dose-dependent increase in GH release, and a dose-dependent decrease in PRL release. Melatonin effects were abolished upon addition of luzindole, a melatonin antagonist. Our results provide the first evidence that melatonin modulates GH and PRL secretion in Teleost fish pituitary. Melatonin effects on GH have never been reported in any vertebrate before. The effects result from a direct action of melatonin on pituitary cells. The complexity of the observed responses suggests several types of melatonin receptors might be involved.

PMID: 12960030 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12960009&dopt=Abstract

Endocrinology. 2003 Sep 4 [Epub ahead of print].

Photoperiodic regulation of hypothalamic retinoid signalling: association of RXR{gamma} with body weight.

Ross AW, Webster CA, Mercer JG, Moar KM, Ebling FJ, Schuhler S, Barrett P, Morgan PJ.

Molecular Endocrinology Group, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, Scotland, U.K, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, U.K.

This study reports novel events related to photoperiodic programing of the neuroendocrine hypothalamus. To investigate photoperiod responsive genes, Siberian hamsters were maintained in long or short photoperiods that generate physiological states of obesity or leanness. Microarray expression analysis first identified CRBP1 as a photoperiod-responsive gene, then further studies using in situ hybridization and immunocytochemistry revealed that expression levels of several related retinoid-signaling genes were modulated in response to photoperiod changes. Genes of the retinoid-signaling pathway, encoding nuclear receptors (RXR/RAR) and retinoid binding proteins (CRBP1 and CRABP2) are photoperiodically-regulated in the dorsal tuberomammillary nucleus (DTM): their expression is significantly lower in short photoperiods and parallels body weight decreases. Studies in pinealectomized hamsters confirm that the pineal melatonin rhythm is necessary for these seasonal changes, and studies in testosterone-treated hamsters reveal that these changes in gene expression are not the secondary consequence of photoperiod-induced changes in steroid levels. Comparative studies using Syrian hamsters, which show divergent seasonal body weight responses to Siberian hamsters when exposed to short photoperiods, showed a distinct pattern of changes in retinoid gene expression in the DTM in response to a change in photoperiod. We infer that the DTM may be an important integrating center for photoperiodic control of seasonal physiology and suggest that the changes in RXRgamma expression may be associated with seasonal changes in body weight and energy metabolism.

PMID: 12960009 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12932850&dopt=Abstract

Brain Res. 2003 Sep 12;984(1-2):160-9.

PACAP-containing intrapineal nerve fibers originate predominantly in the trigeminal ganglion: a combined retrograde tracing- and immunohistochemical study of the rat.

Moller M, Baeres FM.

Institute of Medical Anatomy, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark

Pituitary adenylate-cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated from the hypothalamus and located in many neuronal systems in both the central and peripheral nervous system. PACAP is also found in nerve fibers innervating the pineal gland, where it stimulates the secretion of the pineal hormone, melatonin, by binding to specific PACAP-receptors located on the cell membrane of the pinealocyte. In this study we have investigated the origin of PACAP-containing nerve fibers innervating the rat pineal gland by combined retrograde tracing with Fluorogold and immunohistochemistry for PACAP. A solution of 2% Fluorogold was injected iontophoretically into the superficial pineal gland of Wistar rats, and the animals were allowed to survive for 1 week. After perfusion fixation of the rats, the location of the tracer was investigated in the brain and the sphenopalatine, otic, and trigeminal ganglia. The tracer was found in all the investigated ganglia. However, colocalization with PACAP was predominantly found in the trigeminal ganglion and only occasionally in the sphenopalatine and otic ganglia. Due to the stimulatory function of PACAP on pineal melatonin secretion, the PACAP-containing neurons of this ganglion could be considered a subset of the parasympathetic nervous system. The presence of neurons with a parasympathetic function in a ganglion that has been considered a purely sensory ganglion, is a new concept in neuroanatomy.

PMID: 12932850 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12932203&dopt=Abstract

J Pineal Res. 2003 Oct;35(3):188-95.

Quantitative differences in the pineal ultrastructure of perinatal and adult harp (Phoca groenlandica) and hooded seals (Cystophora cristata).

Aarseth JJ, Stokkan KA.

Department of Arctic Biology and Institute of Medical Biology, University of Tromso, Tromso, Norway.

Seals are unique among mammals in that newborns have a large pineal gland and extremely high plasma levels of melatonin at birth. Melatonin levels are also high in the seal fetus but decline rapidly during the first few days of life. The aim of the present study was to provide quantitative information about the ultrastructure of the seal pineal gland using fetal, newborn, and adult hooded seals (Cystophora cristata), and newborn and adult harp seals (Phoca groenlandica). The relative and absolute volumes of pinealocytes (Pi), arteries and veins, nerves, connective tissue, capillaries and glial cells, as well as mitocondria and lipid droplets in Pi, were calculated by use of point count analysis. Whereas the pineal ultrastructure was similar in fetuses and newborns, both seal species showed a pronounced and particular reduction in the volume of Pi and a similar reduction in pinealocyte mitochondria. There was also a shift from unmyelinated to myelinated pineal nerves in adults compared with fetal/newborns. The selective and marked reduction of Pi may explain the zonated pineal structure typical of the adult seal. The results demonstrate that the fetal gland is as large and active as that of the newborn seal and support the notion that the large size and high activity of the pineal gland in the newborn seal is a fading consequence of its prenatal condition.

PMID: 12932203 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12932204&dopt=Abstract

J Pineal Res. 2003 Oct;35(3):196-203.

Analysis of gene expression following norepinephrine stimulation in the rat pineal gland using DNA microarray technique.

Fukuhara C, Dirden JC, Tosini G.

Neuroscience Institute and NSF Center for Behavioral Neuroscience, Morehouse School of Medicine, Atlanta, GA, USA.

Several studies have demonstrated that norepinephrine (NE) is the critical neurotransmitter for the regulation of gene expression in the pineal gland. We studied the acute effect of NE stimulation in cultured rat pineal glands using Affymetrix rat genome microarray GeneChip probe arrays. Our data demonstrate that NE stimulation affects regulation of several genes; 44 and 29 genes were up- or down-regulated more than 2.5-fold, respectively. As shown in previous studies, arylalkylamine N-acetyltransferase, cyclic AMP responsive element modulator, jun-B and c-fos mRNA levels were increased by NE stimulation. Genes that were not previously reported and increased by NE stimulation in the pineal gland were protein tyrosine phosphatase, nuclear receptors, and activity and neurotransmitter-induced early genes. Unlike up-regulated genes, most of the down-regulated genes were not reported previously. Genes encoding enzymes involved in metabolism and structural proteins were decreased following NE stimulation. Identification of genes affected by NE stimulation would provide valuable information to understanding pineal biology fully.

PMID: 12932204 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12948253&dopt=Abstract

J Med Assoc Thai. 2003 Jul;86(7):603-11.

Intracranial germ cell tumors: experience in King Chulalongkorn Memorial Hospital.

Shotelersuk K, Rojpornpradit P, Chottetanaprasit T, Lertbutsayanukul C, Lertsanguansinchai P, Khorprasert C, Asavametha N, Suriyapee S, Jumpangern C.

Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

A retrospective study was performed on 69 patients with intracranial germ cell tumors who were treated at the Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital from 1990 to 2000. Median age was 15 years. Forty-two cases (60.87%) had histologically confirmed germinoma or nongerminomatous germ cell tumors. Germinoma was the predominate histology followed by mixed germ cell tumors. Pineal and suprasellar regions were the two leading sites, hydrocephalus (85.5%) and diplopia (57.97%) were the two most common clinical presentations. Only 13 cases had the result of cerebrospinal fluid (CSF) cytology or magnetic resonance imagine (MRI) of the spine before initial treatment. Serum tumor markers, Alpha fetoprotein and beta-human chorionic gonadotropin, were available in 66.67 per cent. Total or partial tumor removal were feasible in 24 cases. Whole brain irradiation was given in almost all cases with the median dose of 3,600 cGy. The median total tumor dose was 5,400 cGy. Whole spine radiation was utilized in 17 cases. The mean follow-up time was 41 months. The five-year disease free survival was 73.59 per cent. Overall 3 and 5 year survival rates were 86.45 per cent and 81.64 per cent, respectively.

PMID: 12948253 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12960008&dopt=Abstract

Endocrinology. 2003 Aug 28 [Epub ahead of print].

Expression of Circadian Rhythm Genes in GnRH-Secreting GT1-7 Neurons.

Gillespie JM, Chan BP, Roy D, Cai F, Belsham DD.

Departments of Physiology, Institute of Medical Science, Obstetrics and Gyneacology, and Medicine, University of Toronto and Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada M5S 1A8.

The center for circadian rhythms in mammals is the suprachiasmatic nucleus (SCN) of the hypothalamus, composed of single cell circadian oscillators driven by a transcriptional/translational feedback loop where clock proteins drive clock gene expression. These genes are expressed in peripheral tissues, and several brain areas outside the SCN. It is likely that some peripheral oscillators are synchronized by the SCN. The pineal hormone melatonin plays an important role in the entrainment of circadian rhythms, through feedback to the SCN. Melatonin also plays a role in reproduction, including direct effects on GnRH-secreting GT1-7 neurons. The intrinsic rhythmicity of GnRH neurons suggests that these neurons may express the components of the circadian oscillator. Using the GT1-7 cell line, we demonstrate expression the circadian rhythm genes, clock, BMAL1, timeless (tim), period1 (per1), period2 (per2), cryptochrome1 (cry1) and cryptochrome2 (cry2). Furthermore, semi-quantitative RT-PCR demonstrates that BMAL1, per1, and per2, as well as GnRH mRNAs are expressed with a circadian-like rhythm after synchronization over 54 h. With available antibodies, we demonstrated CLOCK, BMAL1, and PERIOD1 protein expression in these cells, with BMAL1 protein levels showing a rhythmic expression pattern. In addition, receptors for melatonin, mt1 and MT2, also show a circadian expression pattern in the GT1-7 cells and their expression is downregulated by melatonin treatment. These findings suggest that the components of the clock machinery in mammals may play a role in GnRH neuronal function.

PMID: 12960008 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12937686&dopt=Abstract

Bull Exp Biol Med. 2003 Jun;135(6):603-607.

Ultrastructure of the Pineal Gland after gamma-Irradiation under Conditions of Inhibition of Adrenocortical Function.

Popuchiev VV, Yakovleva ND, Konoplyannikov AG, Kvetnoi IM, Kita K, Kita I.

Medical Radiology Research Center, Russian Academy of Medical Sciences, Obninsk; St. Petersburg Institute of

Bioregulation and Gerontology, North-Western Division of Russian Academy of Medical Sciences; Institute of Industrial Organic Chemistry, Poland. popoutch@mrrc.obninsk.ru
Electron microscopy showed that whole-body gamma-irradiation in sublethal doses led to the appearance of injuries in pinealocytes, glial cells, and vessels of the pineal gland in rats. Limitation of the nonspecific effect of gamma-irradiation via inhibition of adrenocortical function with metopirone in physiological doses reduced the radiation-induced ultrastructural damage to the pineal gland.

PMID: 12937686 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12971991&dopt=Abstract

Gene Expr Patterns. 2003 Oct;3(5):591-4.

Expression of ric-8 (synembryn) gene in the nervous system of developing and adult mouse.

Tonissoo T, Meier R, Talts K, Plaas M, Karis A.

Department of Integrative Zoology, University of Tartu, 46 Vanemuise St., 51014, Tartu, Estonia

Recent biochemical studies revealed that ric-8A encodes a guanine nucleotide exchange factor for a subset of Galpha proteins. Ric-8 is a key component of a signaling network in C. elegans that regulates neurotransmitter secretion and also plays a role in centrosome-mediated events during early embryogenesis. Here we show that during the early development in mice (E9.5-E12.0) ric-8 (synembryn) is expressed in the developing nervous system such as the cranial ganglia, neural tube, sympathetic chain and dorsal root ganglia. Ric-8 is also found in the lens, vomeronasal organ, and endolymphatic sac. In adult brain, it is expressed in the neocortex, hippocampus, and cerebellum as well as in the pineal gland and ependymal layer.


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12943195&dopt=Abstract

J Enzyme Inhib Med Chem. 2003 Apr;18(2):119-25.

Design, synthesis and in vitro evaluation of novel benzo[b]thiophene derivatives as serotonin N-acetyltransferase (AANAT) inhibitors.

Mesangeau C, Yous S, Chavatte P, Ferry G, Audinot V, Boutin JA, Delagrange P, Bennejean C, Renard P, Lesieur D.

Laboratoire de Chimie Therapeutique, Faculte des Sciences Pharmaceutiques et Biologiques, BP 83, 59006 Lille Cedex, France.

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is the penultimate enzyme in melatonin (5-methoxy-N-acetyltryptamine) biosynthesis. It is the key-enzyme responsible of the nocturnal rhythm of melatonin production in the pinea
l gland. Specific AANAT inhibitors could be useful for treatment of different physiopathological disorders encountered in diseases such as seasonal affective disorders or obesity. On the basis of previous works and 3D-QSAR studies carried out in our laboratory, we have synthesized and evaluated four novel benzo[b]thiophene derivatives designed as AANAT inhibitors. Compound 13 exhibited high inhibitory activity (IC50 = 1.4 microM) and low affinities for both MT, (1100 nM) and MT2 (1400 nM) receptors.

PMID: 12943195 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12956958&dopt=Abstract

Curr Biol. 2003 Sep 2;13(17):1543-8.

Photoperiod differentially regulates circadian oscillators in central and peripheral tissues of the Syrian hamster.

Carr AJ, Johnston JD, Semikhodskii AG, Nolan T, Cagampang FR, Stirland JA, Loudon AS.

School of Biological Sciences, University of Manchester, Oxford Road, M13 9P, Manchester, United Kingdom

In many seasonally breeding rodents, reproduction and metabolism are activated by long summer days (LD) and inhibited by short winter days (SD). After several months of SD, animals become refractory to this inhibitory photoperiod and spontaneously revert to LD-like physiology. The suprachiasmatic nuclei (SCN) house the primary circadian oscillator in mammals. Seasonal changes in photic input to this structure control many annual physiological rhythms via SCN-regulated pineal melatonin secretion, which provides an internal endocrine signal representing photoperiod. We compared LD- and SD-housed animals and show that the waveform of SCN expression for three circadian clock genes (Per1, Per2, and Cry2) is modified by photoperiod. In SD-refractory (SD-R) animals, SCN and melatonin rhythms remain locked to SD, reflecting ambient photoperiod, despite LD-like physiology. In peripheral oscillators, Per1 and Dbp rhythms are also modified by photoperiod but, in contrast to the SCN, revert to LD-like, high-amplitude rhythms in SD-R animals. Our data suggest that circadian oscillators in peripheral organs participate in photoperiodic time measurement in seasonal mammals; however, circadian oscillators operate differently in the SCN. The clear dissociation between SCN and peripheral oscillators in refractory animals implicates intermediate factor(s), not directly driven by the SCN or melatonin, in entrainment of peripheral clocks.

PMID: 12956958 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12920545&dopt=Abstract

Childs Nerv Syst. 2003 Aug 14 [Epub ahead of print].

Pineal cysts in childhood.

Mandera M, Marcol W, Bierzynska-Macyszyn G, Kluczewska E.

Division of Pediatric Neurosurgery, Department of Pediatric Surgery, Silesian University School of Medicine, ul. Medykow 16, 40-752, Katowice, Poland.

INTRODUCTION. Little is known about the incidence and symptomatology of pineal cysts in children. Until now, the proper management of this group of patients has not been established.
PURPOSE. The purpose of this study was to evaluate the epidemiological and clinical features of pineal cysts in children and adolescents and to try to find guidelines for their management.
METHODS AND RESULTS. We analyzed 24 patients (17 girls, mean age 9, and 7 boys, mean age 14) with pineal cysts found as the only pathology on MRI. Six patients were treated surgically (excision of the cysts via a supracerebellar-infratentorial approach) because of the progression of neurological symptoms or the enlargement of the cyst at follow-up. In this group of patients, no surgery-related complications were noted, nor was residual cyst observed on postoperative MRI. In 4 cases, histological examination revealed simple cysts, but in 2 cases pineocytomas were diagnosed. Preoperative symptoms disappeared except light headache in 2 cases and in 1 case no improvement was obtained. The remaining 18 patients had a mean follow-up of 38 months (range 24-60 months). None of the cysts diminished or collapsed. We also measured the circadian pattern of melatonin secretion as well as beta-HCG and AFP levels in serum before surgery. We found very high night levels of melatonin in both of the patients with pineocytomas, while the patients with pineal cysts showed normal or depressed melatonin secretion profile.
CONCLUSION. We concluded that though most pineal cysts were clinically benign they should be followed up for many years. If the cyst grows larger in follow-up MRI study and neurological symptoms are progressive, surgical treatment should be performed. In the authors' opinion, one of the markers discriminating benign and neoplastic lesions may be melatonin.

PMID: 12920545 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12916721&dopt=Abstract

Chronobiol Int. 2003 Jul;20(4):697-710.

The circadian system and melatonin: lessons from rats and mice.

Korf HW, Von Gall C, Stehle J. Dr.

Senckenbergische Anatomie, Institut fur Anatomie II, Johann Wolfgang Goethe-Universitat Frankfurt, Frankfurt, Germany. korf@em.uni-frankfurt.de

The circadian system (CS) comprises three key components:
(1) endogenous oscillators (clocks) generating a circadian rhythm;
(2) input pathways entraining the circadian rhythm to the astrophysical day; and
(3) output pathways distributing signals from the oscillator to the periphery.
This contribution briefly reviews some general aspects of the organization of the rodent CS and pays particular attention to recent results obtained with various mouse strains, related to molecular mechanisms involved in entraining the endogenous clock and the role of the pineal hormone melatonin as a hand of the endogenous clock.

PMID: 12916721 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12911638&dopt=Abstract

J Neurochem. 2003 Sep;86(5):1308-11.

Comparison of circadian expression of tryptophan hydroxylase isoform mRNAs in the rat pineal gland using real-time PCR.

Sugden D.

Centre for Reproduction, Endocrinology and Diabetes, School of Biomedical Sciences, Kings College London, London, United Kingdom.

A second gene encoding a functional tryptophan hydroxylase activity has recently been described (TPH2), which is expressed abundantly in brainstem, the primary site of serotonergic neurons in the CNS. As serotonin (5-HT) has an important role as a precursor of the nocturnal synthesis of the pineal gland hormone, melatonin, it was of interest to determine the relative expression of TPH1 and 2 mRNA in the rat pineal during the light:dark (L:D) cycle using sensitive real-time RT-PCR assays which were developed for each TPH isoform. TPH1 mRNA expression was 105-fold more abundant in rat pineal than TPH2, and showed a significant approximately 4-fold nocturnal increase in expression which may contribute to the previously described nocturnal increase in pineal tryptophan hydroxylase activity. TPH2 expression within the gland showed no significant variation with time of day and was very low ( approximately 300 copies/gland) indicating expression in the small proportion of 'non-pinealocyte' cells in the gland.

PMID: 12911638 [PubMed - in process]

Full free report available at http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2003000300027&lng=en&nrm=iso

Arq Neuropsiquiatr. 2003 Jun;61(2B):468-72. Epub 2003 Jul 28.

Glioblastoma multiforme of the pineal region: case report.

Gasparetto EL, Warszawiak D, Adam GP, Bleggi-Torres LF, de Carvalho Neto A.

Discipline of Diagnostic radiology, Department of Pathology, , University of Parana school of Medicine, Curitiba PR,l Brazil. gasparetto@hotmail.com

PURPOSE: pineal region tumors are uncommon, and comprise more frequently three categories: germ cell, parenchymal cell and glial tumors. Most pineal gliomas are low-grade astrocytomas. Glioblastoma multiforme, the most aggressive and common brain tumor, is extremely rare at this location with only few cases reported.
CASE DESCRIPTION: a 29-year-old woman with a two month history of headache, nuchal pain, fever, nausea and seizures and physical examination showing nuchal rigidity, generalized hypotony, hypotrophy and hyper-reflexia, Babinski sign and left VI cranial par palsy. CT scan examination revealed a ill-defined hypodense lesion at the pineal region with heterogeneous contrast enhancement. MRI showed a lesion at the pineal region infiltrating the right thalamic region. The patient underwent a right craniotomy with partial resection of the mass. The histological examination of paraffin-embedded material defined the diagnosis of glioblastoma multiforme. Post-operative radiotherapy was indicated but the patient refused the treatment and died two months afterwards.
CONCLUSION: in spite of its rarity at this location, glioblastoma multiforme should be considered in the differential diagnosis of aggressive lesions at the pineal region.

PMID: 12894287 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12887655&dopt=Abstract

J Pineal Res. 2003 Sep;35(2):118-24.

Long-term in vivo pineal microdialysis.

Sun X, Liu T, Deng J, Borjigin J.

Department of Embryology, Carnegie Institution of Washington, Baltimore, MD, USA.

This study describes the development of a new technique for long-term measurement of daily 5-hydroxytryptamine (5-HT) and melatonin contents in the pineal gland of freely moving rats. The technique features a number of novel improvements over previous protocols. It allows visualization of the pineal gland for accurate targeting of the guide cannula, which minimizes bleeding; incurs no direct injury to the surrounding brain tissues; and causes no interference with the sympathetic innervation from the superior cervical ganglia. Robust releases of melatonin and indole precursors were continuously monitored quantitatively and reproducibly for more than 2 wk in the same animal. In addition, effects of pharmacological agents on in vivo pineal circadian rhythms can be studied reproducibly over time, and gene expression profiles can be correlated with physiological consequences in single animals. Using these approaches, it is found that beta-adrenergic activation leads to decreased release of 5-HT, and that increased cAMP signaling in vivo results in activation of N-acetyltransferase gene induction and melatonin production. These studies will enhance the understanding of signaling pathways that regulate pineal 5-HT and melatonin synthesis and secretion.

PMID: 12887655 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12850059&dopt=Abstract

Int J Dev Neurosci. 2003 Aug;21(5):263-6.

Magnetic field exposure during gestation: pineal and cerebral cortex serotonin in the rat.

Canedo L, Cantu RG, Hernandez-R J.

Division de Investigacion, Hospital Juarez, Mexico, DF, Mexico.

Extremely low frequency (ELF) magnetic fields seem to have a reproducible influence on cells in transitional states, such as cells during the embryonic and early postnatal periods. Intense and continuous serotonergic synaptic growth is present during the first 2 weeks of postnatal development, paralleled by 5-HT content in the brain, so, the effect of ELF on 5-HT content in the cerebral cortex and pineal gland was determined in growing rats exposed during pregnancy, and in normal controls. The results showed a significant 5-HT increase at birth, 15 and 21 days, in the cerebral cortex. No differences were found in the pineal gland. These short MF exposures had a long term effect on cerebral cortex 5-HT, possibly starting since the fetal period. The relevance of the present findings are discussed as related to the serotonin trophic role on the brain cortex.

PMID: 12850059 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12881612&dopt=Abstract

Sci STKE. 2003 Jul 22;2003(192):PE29.

Pattern of melatonin secretion mediates transfer of photoperiod information from mother to fetus in mammals.

Goldman BD.

Department of Physiology and Neurobiology, University of Connecticut, U-4156, Storrs, CT 06269, USA. goldman@oracle.pnb.uconn.edu

Studies performed over the past 20 years have revealed that mother rodents can provide photoperiod information to their developing fetuses. In adult mammals, the pattern of pineal melatonin secretion changes in relation to changes in day length, and the melatonin pattern is a key part of the photoperiodic mechanism. Melatonin crosses the placenta, and fetal rodents can respond to the maternal melatonin rhythm. Thus, the mother's melatonin rhythm provides day-length information to the fetus, and this information is used, along with photoperiod information that is obtained after birth, to influence juvenile development. The transfer of photoperiod information from mother to fetus may be part of an adaptive system. When young are born early in the spring or summer breeding season, the increase in day length between the times of fetal and postnatal life results in rapid reproductive maturation, allowing these early-born animals to reproduce later during the same breeding season. In contrast, for young born late in the breeding season, the decrease in photoperiod between fetal and postnatal life results in delayed maturation of the gonads, and reproduction is delayed until the beginning of the next year's breeding season.

PMID: 12881612 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12874384&dopt=Abstract

Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9584-9. Epub 2003 Jul 21.

Bimodal circadian secretion of melatonin from the pineal gland in a living CBA mouse.

Nakahara D, Nakamura M, Iigo M, Okamura H.

Department of Psychology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan; Department of Anatomy, St. Marianna University School of Medicine, Miyamae, Kawasaki 216-8511, Japan.

Circadian melatonin secretion is the best-known output signal from the circadian pacemaker in the suprachiasmatic nucleus that indicates internal conditions of the body. We have established a system that enables long-term monitoring of melatonin secretion by implanting a transverse microdialysis probe in or near the pineal gland in a freely moving mouse. This in vivo method enabled continuous measurement of melatonin secretion over a period of >20 days in individual CBA mice, with simultaneous recording of the locomotor activity. Pineal melatonin secretion was completely matched to the circadian change of locomotor activity, and for the light-induced phase shift, the shift of melatonin secretion was clearer than the shift of locomotor rhythm. This analysis allowed us to detect rhythm with a high sensitivity: two peaks of daily secretion were observed, with the first small peak at the day-night transition time and the second large peak at midnight. The large nighttime peak was suppressed by tetrodotoxin, a Na+ channel blocker, and enhanced by both phenylephrine and isoproterenol, alpha- and beta-adrenergic agonists, whereas daytime melatonin levels were not affected by tetrodotoxin infusion. This finding suggests that, in CBA mice, melatonin release at night is activated by adrenergic signaling from the superior cervical ganglion, but the enhancement of melatonin during daytime is not mediated by neuronal signaling.

PMID: 12874384 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12856801&dopt=Abstract

Endocr Res. 2003 May;29(2):141-56.

The structure of the pineal complex in a common Indian teleost, Catla catla: evidence for pineal-induced inhibition of testicular function within an annual reproductive cycle.

Bhattacharya S, Dey R, Basu A, Maitra SK, Banerji TK.

Department of Zoology, University of Burdwan, Burdwan, India.

The structure of the pineal complex and the annual reproductive cycle in a major Indian carp, Catla catla, were investigated in the present study. Additionally, given the well-known inhibitory effects of the pineal on reproductive function in mammals, attempts were made to investigate whether or not the pineal exerts an inhibitory influence on reproductive function in this piscine species as well. Sexually adult animals were utilized in all experiments. The cytomorphology of the pineal complex and a number of parameters for testicular function--such as testicular cytology, serum testosterone levels, and testicular activities of two steroidogenic enzymes, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) were examined over a period of two years. Our studies showed that the pineal complex in this species consists of three separate but distinctly connected components: (a) an end vesicle (EV); (b) a long pineal stalk (PS); and (c) a dorsal sac (DS). Of these, the epithelial lining of the EV consists of cells that have rounded vesicular nuclei and long apical cytoplasmic processes that reach the lumen, features suggestive of photoreceptor cells. The cells of the PS have some similarity with those of the EV, while DS cells appear columnar and ciliated. With regard to gonadal activity, germ cell profiles revealed that this species has four distinct phases during the annual reproductive cycle: (a) preparatory (January-April); (b) pre-spawning (May-June); (c) spawning (July); and (d) post-spawning (August-December). During the spawning phase (July), seminiferous tubular diameter, percentage of late spermatids within seminiferous tubules, and serum testosterone levels showed the highest values compared to those obtained in most of the other phases of the reproductive cycle. Also in July, along with peak serum testosterone levels, the activities of 17beta-HSD and delta5-3beta-HSD were at their highest levels. In a correlation between the pineal cytology and testicular functional status, it was noted that both the nuclear diameter and the apical cytoplasmic projections of the EV photoreceptor cells showed a significant reduction, thus suggesting a reduced synthetic activity, during the month of July, the spawning phase of the reproductive cycle. In contrast, the same features of the EV cells during the other phases of the reproductive cycle showed an increased cellular and metabolic activity--a time when the gonads were less active and in a quiescent stage. These data suggest an inhibitory role of the pineal on gonadal function and thus provide additional credence to the concept that, as in higher mammals, there exists an inverse relationship between the pineal activity and gonadal function in teleost fishes as well.

PMID: 12856801 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12849888&dopt=Abstract

Pediatr Neurol. 2003 Apr;28(4):310-2.

Parkinsonism as an unusual presenting symptom of pineal gland teratoma.

Dolendo MC, Lin TP, Tat OH, Chong QT, Timothy LK.

Children's Medical Institute, National University Hospital, Singapore

We report a case of a 14-year-old Chinese boy with immature teratoma of the pineal gland who manifested with parkinsonism. Diagnostic evaluation revealed hydrocephalus and an immature teratoma of the pineal gland extending to the thalamus. An urgent ventriculoperitoneal shunt was inserted, and chemotherapy was given to reduce the tumor size. The tumor was completely excised 2 months after diagnosis with improvement of clinical signs and symptoms. His symptoms recurred 3 months later with sudden onset of obtundation, tremors, cogwheel rigidity, and marked bradykinesia. Magnetic resonance imaging (MRI) revealed a small enhancing lesion in the pineal region and progressive hydrocephalus on serial studies. He was treated with carbidopa/levodopa and amantadine, but marked improvement was only observed after reprogramming his VP shunt. Features consistent with the growing teratoma syndrome were noted during this period. These were progressive pineal gland tumor enlargement documented on MRI without increase in previously elevated alpha-fetoprotein levels. The tumor continued to enlarge despite gamma knife radiosurgery. Secondary parkinsonism is a rare presentation of pineal gland tumors and has not been reported in association with the growing teratoma syndrome.

PMID: 12849888 [PubMed - in process]

Int J Dev Neurosci. 2003 Aug;21(5):263-266.

Magnetic field exposure during gestation: pineal and cerebral cortex serotonin in the rat.

Canedo L, Cantu RG, Hernandez-R J.

Division de Investigacion, Hospital Juarez, DF, Mexico, Mexico

Extremely low frequency (ELF) magnetic fields seem to have a reproducible influence on cells in transitional states, such as cells during the embryonic and early postnatal periods. Intense and continuous serotonergic synaptic growth is present during the first 2 weeks of postnatal development, paralleled by 5-HT content in the brain, so, the effect of ELF on 5-HT content in the cerebral cortex and pineal gland was determined in growing rats exposed during pregnancy, and in normal controls. The results showed a significant 5-HT increase at birth, 15 and 21 days, in the cerebral cortex. No differences were found in the pineal gland. These short MF exposures had a long term effect on cerebral cortex 5-HT, possibly starting since the fetal period. The relevance of the present findings are discussed as related to the serotonin trophic role on the brain cortex.

PMID: 12850059 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12844242&dopt=Abstract

Urol Res. 2003 Jul 3 [Epub ahead of print].

Melatonin attenuates alpha-adrenergic-induced contractions by increasing the release of vasoactive intestinal peptide in isolated rat penile bulb.

Olmez E, Kurcer Z.

Department of Pharmacology, Faculty of Medicine, Inonu University, 44069, Malatya, Turkey.

The effects of melatonin on alpha-adrenergic-induced contractions caused by electrical field stimulation (EFS) or the alpha(1)-adrenoceptor agonist phenylephrine (Phe) were investigated in isolated rat penile bulb. Melatonin as well as melatonin receptor agonists N-acetylserotonin and 2-iodomelatonin and melatonin antagonist luzindole attenuated the EFS-induced contractions and the concentration-response curve to Phe. The effect of melatonin on Phe-induced contractions was completely reversed by treatment with tetrodotoxin, guanethidine or vasoactive intestinal peptide (VIP) antagonist. On the other hand, pretreatment with N-methyl-l-arginine, atropine, and luzindole did not reverse the effect of melatonin. Thus, we demonstrated that melatonin at nanomolar concentrations inhibits the alpha-adrenergic responses in isolated rat penile bulb. Since alpha-adrenoceptor blocking agents are known to interfere with detumescence of the erect penis, serum levels or administration of this pineal hormone may affect erectile function. This effect of melatonin may be the result of its allosteric interaction with the presynaptic receptors on VIPergic neurons, which are affected by sympathetic transmission, and then an increase in VIP release from these neurons.

PMID: 12844242 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12836064&dopt=Abstract

Amino Acids. 2003 Jul;25(1):95-105.

Characterization of tryptophan high affinity transport system in pinealocytes of the rat. Day-night modulation.

Gutierrez CI, Urbina M, Obregion F, Glykys J, Lima L.

Laboratorio de Neuroquimica, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas, Venezuela.

Tryptophan is required in the pineal gland for the formation of serotonin, precursor of melatonin biosynthesis. The level of this amino acid in the serum and in the pineal gland of the rat undergoes a circadian rhythm, and reduced plasma tryptophan concentration decreases secretion of melatonin in humans. Tryptophan is transported into the cells by the long chain neutral amine acid system T and by the aromatic amino acid system T. The high affinity component of [(3)H]tryptophan uptake was studied in pinealocytes of the rat. Inhibition was observed in the presence of phenylalanine or tyrosine, but not in the presence of neutral amino acids, alanine, glycine, serine, lysine or by 2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid, a substrate specific for system L. The transport of tryptophan was temperature-dependent and trans-stimulated by phenylalanine and tyrosine, but was energy-, sodium-, chloride-, and pH-independent. In addition, the sulphydryl agent N-ethylmaleimide did not modify the high affinity transport of tryptophan in pinealocytes. The kinetic parameters were not significantly different at 12:00 as compared to 24:00 h. The treatment with the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine, produced an increase in the maximal velocity of the uptake and a reduction in the affinity at 12:00, but not at 24:00 h, probably indicating that during the day, the formation of serotonin in the pineal gland is favoured by elevating the uptake of tryptophan, whereas at 24:00 h other mechanisms, such as induction of enzymes are taking place. High affinity tryptophan uptake in the rat pineal gland occurs through system T and is upregulated during the day when the availability of serotonin is reduced.

PMID: 12836064 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12823613&dopt=Abstract

Pineal Res. 2003 Aug;35(1):45-53.

Regional heterogeneity in immunoreactive macrophages/microglia in the rat pineal gland.

Jiang-Shieh YF, Wu CH, Chang ML, Shieh JY, Wen CY.

Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan Taiwan; Department and Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Using specific macrophage antibodies (OX-42, OX-6, ED-1 and ED-2), this study examined the distribution of macrophages/microglia in the pineal gland of adult rats. Except for ED-2, all antibodies labeled distinct subpopulations of macrophages/microglia in the gland; ED-2 labeling was hardly detectable. The quantitative study showed that the pineal macrophages/microglia (PMM) expressing complement type 3 receptors (OX-42) were more numerous than those expressing the major histocompatibility complex class II antigen (OX-6) or unknown cytoplasmic/lysosomal antigens (ED-1). The PMM were ubiquitous, especially the OX-42 labeled cells which were distributed from the dorsal to the ventral aspect of the gland. The macrophages/microglia labeled with OX-6 or ED-1 were localized mainly in the intermediate portion of the pineal gland. Immunolabeled cells were sparsely distributed in the distal portion of the pineal gland. A notable feature was that the OX-6 labeled macrophages/microglia showed a proximal-distal gradient in cell density. Another interesting feature was the occurrence of prominent cell aggregations around the larger blood vessels. These cells were mostly round and exhibited different immunoreactivity. Confocal microscopic study with triple immunolabeling further revealed that individual PMM cell possessed two or more different antigens (ED-1+/OX-6+, OX-42+/OX-6+ or OX-42+/ED-1+). Remarkably, a large population co-expressed ED-1+/OX-6+/OX-42+. The present results show that the expression of immunoreactive molecules in PMM varies in topographical distribution of the cells. It is suggested that this may be linked to their immunoregulatory functions in the gland.

PMID: 12823613 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787552&dopt=Abstract

Best Pract Res Clin Endocrinol Metab. 2003 Jun;17(2):273-85.

Melatonin: clinical relevance.

Reiter RJ.

Department of Cellular and Structural Biology, Mail Code 7762, The University of Texas Health Science Center, 7703 Floyd Curl Drive, 78229-3900, San Antonio, TX, USA

This chapter reviews the neural connections between the retinas and the pineal gland and summarizes the role of the light:dark cycle and the biological clock, i.e. the suprachiasmatic nuclei, in regulating pineal melatonin synthesis and secretion. The cellular mechanisms governing the nocturnal production of melatonin are described together with the way in which the misuse of light interferes with the circadian melatonin cycle and the total quantity of the indole generated. The chapter describes the nature of the membrane melatonin receptors and their signal transduction mechanisms in peripheral organs. The clinical implications and potential uses of melatonin in terms of influencing the biological clock (e.g. sleep and jet lag), immune function, and cancer initiation and growth are noted. Additionally, the chapter includes a description of the newly discovered free radical scavenging and antioxidant activities of melatonin; it also includes a list of clinical situations in which melatonin has been used with beneficial effects.

PMID: 12787552 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12791421&dopt=Abstract

Crit Rev Oncol Hematol. 2003 Jun;46(3):221-34.

The role of pineal gland in breast cancer development.

Anisimov VN.

Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, 197758, St. Petersburg, Russia

The role of the modulation of the pineal gland function in development of breast cancer is discussed in this review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits mammary carcinogenesis in pinealectomized rats, in animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen. Pineal peptide preparation Epithalamin and synthetic tetrapeptide Epitalon (Ala-Glu-Asp-Gly) are potent inhibitors of mammary carcinogenesis in rodents and might be useful in the prevention of breast cancer in women at risk.

PMID: 12791421 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12784853&dopt=Abstract

Comp Med. 2003 Apr;53(2):186-90.

Physiologic melatonin concentration, omega-3 fatty acids, and conjugated linoleic acid inhibit fatty acid transport in rodent hind limb skeletal muscle in vivo.

Dauchy RT, Blask DE, Sauer LA, Davidson LK, Krause JA, Smith LC, Dauchy EM.

Laboratory of Experimental Neuroendocrinolgy/Oncology, Bassett Research Institute, Cooperstown, New York 13326-1394, USA.

Melatonin (MLT)
, the circadian neurohormone secreted by the pineal gland in mammals during darkness, eicosapentanoic acid (EPA), and conjugated linoleic acid (CLA) have established regulatory roles in cancer growth. Investigations in our laboratory have indicated that these agents inhibit fatty acid (FA) transport by tumors and several sub-types of white adipose tissue via inhibitory G protein-coupled receptor mechanisms. Skeletal muscle constitutes over 45% of human body mass and plays an important role in cancer cachexia and obesity-related diseases. Since fatty acid oxidation is a major source of energy for this tissue, we tested the hypothesis that physiologic MLT levels, EPA, or CLA injected intravenously, inhibit FA uptake in rat skeletal muscle in vivo. We used a surgical technique for catheterizing the femoral vein in rats that allows rapid blood collection from the entire hind limb, while ensuring continuous blood flow to the tissue. Blood acid/gas tensions and hematocrit were monitored and remained constant during the course of each experiment. The MLT, EPA, and CLA inhibited FA uptake by the tissue and lowered cAMP values. Glucose uptake and glycerol production in the hind limb were not affected. These investigations suggest a novel role for MLT, omega-3 FAs, and CLA in the regulation of FA transport and fat metabolism in skeletal muscle.

PMID: 12784853 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12733707&dopt=Abstract

Endocr J. 2003 Feb;50(1):37-43.

Pineal gland (melatonin) affects the parturition time, but not luteal function and fetal growth, in pregnant rats.

Takayama H, Nakamura Y, Tamura H, Yamagata Y, Harada A, Nakata M, Sugino N, Kato H.

Reproductive, Pediatric and Infectious Science, Perinatal Care Center, Yamaguchi University School of Medicine, 1-1-
1, Minami-Kogushi, Ube 755-8505 Japan.

The purpose of the present study was to investigate the role of pineal gland (melatonin) on parturition time, luteal function, and fetal growth in pregnant rats. Cycling rats were subjected to pinealectomy or sham operation under ether anesthesia; and pinealectomized rats immediately underwent implantation of a melatonin capsule (PINX + Mel group) or a vehicle-containing capsule (PINX group), and sham operated rats also underwent implantation of a vehicle-containing capsule (control group). All rats were maintained under the same photoperiod conditions (14 L:10 D) and were induced pregnancy. Blood samples were obtained on days 7, 12, 15, 17, 19, and 21 of pregnancy to measure serum progesterone concentrations, and parturition times were recorded on days 22 and 23. In the next experiment, pregnant PINX rats received subcutaneous injection of melatonin (10 microg/body) at 08:00 h (PINX + 8 h group) or at 20:00 h (PINX + 20 h group) from day 15 to the end of pregnancy, and parturition times were recorded. Parturition times of rats in the PINX group, the PINX + Mel group or the PINX + 8 h group, but not the PINX + 20 h group, were significantly different compared with those in the control group. Pinealectomy or melatonin implantation did not affect serum progesterone concentrations during pregnancy or the number and weight of fetuses or corpora lutea. The present results indicate that pineal gland (melatonin rhythm) synchronizing with photoperiodic rhythm is likely to be an important determinant of parturition time, but it does not affect progesterone production or fetal growth in pregnant rats.

PMID: 12733707 [PubMed - in process]
Note from FAN: definition of Parturition: Childbirth [to be in labor].

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12700404&dopt=Abstract

Toxicol Sci. 2003 Jun;73(2):416-22. Epub 2003 Apr 15.

In vivo and in vitro effects of melatonin or ganglioside GT1B on L-cysteine-induced brain mitochondrial DNA damage in mice.

Yamamoto HA, Mohanan PV.

The University of Tsukuba, Institute of Community Medicine, Tsukuba, Ibaraki, 305-8575 Japan. hiro_aki@d4.dion.ne.jp

The effects of L-cysteine on mitochondrial DNA (mtDNA) in mouse brain were investigated both in vivoandin vitro. An intracerebroventricular (icv) injection of L-cysteine (1.25 micromol/animal) caused mtDNA damage in brain frontal and central portions of the cortex, broad-spectrum limbic and severe sustained seizures in mice, and increased lipid peroxidation in the whole brain. The L-cysteine-mediated effects were prevented by an intraperitoneal (ip) preinjection of melatonin (20 mg/kg) or an intracerebroventricular preinjection of ganglioside GT1b (90 nmol/animal). Furthermore, in in vitroexperiments, L-cysteine (0.05, 0.5, or 1.0 mM) caused damage to brain mtDNA and increased lipid peroxidation in a concentration-dependent manner when incubated at 37 degrees C for 20 or 60 min with a homogenate prepared from whole mouse brains. However, the mtDNA damage and the increased lipid peroxidation were completely abolished by a cotreatment with melatonin (1.5 mM), a potent scavenger of the hydroxyl radical (*OH), or ganglioside GT1b (60 microM), a potent inhibitor of glutamate-receptor-mediated activation and translocation of protein kinase C and lipid peroxidation. These results suggest that reactive oxygen species including the *OH may be involved in l-cysteine-induced brain mtDNA damage, lipid peroxidation, and development of seizures in mice. Therefore, we concluded that *OH scavengers, such as the pineal hormone melatonin and ganglioside GT1b, can protect against brain mtDNA damage, seizures, and lipid peroxidation induced by reactive oxygen species producers such as L-cysteine.

PMID: 12700404 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12722927&dopt=Abstract

Neuropathology. 2003 Mar;23(1):57-60.

Lung carcinoma metastasis presenting as a pineal region tumor.

Kakita A, Kobayashi K, Aoki N, Eguchi I, Morita T, Takahashi H.

Department of Pathology, Brain Research Institute, Niigata University, Japan. kakita@bri.niigata-u.ac.jp

An autopsy case is reported of pineal metastasis from lung adenocarcinoma, which is a rare manifestation of the disease. A 75-year-old man who had been found to have a lesion in the lung by chest CT 2 years previously, became aware of head heaviness and then suffered consciousness disturbance. Brain MRI revealed a solitary mass in the pineal region with hydrocephalus. At autopsy a midsagittal section of the brain disclosed a well-circumscribed mass consisting of epithelial cells occupying the third ventricle. Although it should be recognized that such metastasis is very rare, the present case provides further information that might be useful for diagnosis.

PMID: 12722927 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12697297&dopt=Abstract

Neurosci Lett. 2003 May 8;341(3):259-61.

Melatonin receptor expression in rat cerebral artery.

Chucharoen P, Chetsawang B, Srikiatkhachorn A, Govitrapong P.

Neuro-Behavioral Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakornpathom 73170, Thailand.

Melatonin has been shown to act on certain vascular beds. However, the identity of melatonin receptors in the cerebral artery has not been established. In the present study, we have attempted to identify melatonin receptor mRNAs of rat cerebral artery by using a reverse transcriptase polymerase chain reaction technique. Total RNAs were extracted from the cerebral artery and different regions of male Sprague-Dawley rats. Amplification of RNAs from pineal gland, hypothalamus and cerebral artery with mt(1) while amplification of RNAs from pineal gland and hypothalamus with mt(2) primers resulted in products of the predicted lengths. The result indicated that mt(1) but not mt(2) melatonin receptor was expressed in the rat cerebral artery, whereas abdominal aorta did not express any type of melatonin receptor. Further studies are necessary to understand the significance of this receptor in regulating physiological function.

PMID: 12697297 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12662960&dopt=Abstract

Clin Radiol. 2003 Apr;58(4):336-7.

No Abstract available

Pineal gland calcification in sub-saharan Africa.

Akano A, Bickler SW.

PMID: 12662960 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12797535&dopt=Abstract

Anat Histol Embryol. 2003 Apr;32(2):124-5.

Arterial vascularization of the pineal gland in the fetus of Zavot-bred cattle.

Aslan K, Ozcan S, Aksoy G, Kurtul I, Dursun N. Kafkas

Universitesi, Veteriner Fakultesi, Anatomi Anabilim Dali, Kars, Turkey. kadiraslan1960@yahoo.com
This study aimed at revealing arterial vascularization of the pineal gland of the Zavot-bred foetus.

Twenty foetuses, regardless of their sex, at the age of 2-7 months were used. Coloured-latex was injected by way of both the right and left common carotid arteries. Then, dissection was performed and vessels nourishing the pineal gland were documented. The pineal gland is vascularized by a number of 2-5 central rami. A small vessel arising from each of the central rami in two foetuses (10%) was shown anastomosing with a branch of the cranial cerebral artery, which advances in cranio-caudal direction in the callosal groove. Hence, anastomoses were observed between several sub-branches of each caudal cerebral and cranial cerebellar arteries.

PMID: 12797535 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12823609&dopt=Abstract

J Pineal Res. 2003 Aug;35(1):16-23.

Identification of dopamine transporter in bovine pineal gland using [3H]GBR 12935.

Govitrapong P, Vilaipun P, Ebadi M.

Department of Pharmacology, Physiology and Therapeutics, School of Medicine & Health Sciences, University of North Dakota, Grand Forks, North Dakota 58203, USA; Neuro-Behavioural Biology Center, Institute of Science and technology for Research and Development, Mahidol University, Salaya, Nakornpathom, 73170, Thailand.

The mammalian pineal gland contains several neurotransmitters and receptors for amino acids, biogenic amines, and peptides. Some of these, such as D1 and D2 dopamine receptors, have been previously identified and characterized in the bovine pineal gland by our group. As a matter of fact, the density of D1 dopamine receptors in the pineal gland is higher than that of corpus striatum, suggesting that this organ must possess a high affinity dopamine transporter, which has been identified in this study by using [3H]GBR 12935 as a radiological ligand and nomifensine to determine non-specific binding. The association rate of [3H]GBR 12935 binding to the pineal membrane was examined as a function of time. The binding reached equilibrium within 45 min of incubation at 25 degrees C. The specific binding was reversible and saturable. The dissociation time course of the specific [3H]GBR 12935 binding from the bovine pineal membrane was also studied. A half-life (t1/2) of 14-min was obtained. The saturation analysis of the [3H]GBR 12935 binding revealed a dissociation equilibrium constant (Kd) of 6.0 +/- 0.9 nm and a receptor density (Bmax) of 6.9 +/- 0.3 pmol/mg protein, which were comparable with those values obtained from bovine striatum and frontal cortex. In competitive experiments, the concentrations of drugs required to inhibit 50% of the binding (IC50) were in descending order GBR 12909 > GBR 12935 > trans-flupenthixol > nomifensine > cis-flupenthixol > amitriptyline > imipramine > desipramine > dopamine > fluoxetine > fuvoxamine > d-amphetamine. However, nisoxetine, SCH 23390, norepinephrine, and serotonin were unable to displace [3H]GBR binding. These results show that drugs capable of blocking dopamine transporters were effective in displacing [3H]GBR binding; whereas specific norepinephrine and serotonin transporter inhibitors were less effective or ineffective. In addition, the dopamine transporter is ion-dependent as sodium increased [3H]GBR binding in a concentration related manner. These results indicate that a high affinity dopamine transporter exists in the bovine pineal, which may exhibit circadian periodicity, and whose physiological functions need to be delineated and characterized in future investigations.

PMID: 12823609 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12622836&dopt=Abstract

J Neuroendocrinol. 2003 Apr;15(4):370-7.

14-3-3 proteins in pineal photoneuroendocrine transduction: how many roles?

Klein DC, Ganguly S, Coon SL, Shi Q, Gaildrat P, Morin F, Weller JL, Obsil T, Hickman A, Dyda F.

Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development/NIH 49/6A82, Bethesda, MD 20892-4480, USA. klein@helix.nih.gov

Recent studies suggest that a common theme links the diverse elements of pineal photoneuroendocrine transduction--regulation via binding to 14-3-3 proteins. The elements include photoreception, neurotransmission, signal transduction and the synthesis of melatonin from tryptophan. We review general aspects of 14-3-3 proteins and their biological function as binding partners, and also focus on their roles in pineal photoneuroendocrine transduction.

Publication Types: Review Review, Tutorial

PMID: 12622836 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485369&dopt=Abstract

J Pineal Res 2003 Jan;34(1):32-35

Different responsiveness of central nervous system tissues to oxidative conditions and to the antioxidant effect of melatonin.

Kaptanoglu E, Palaoglu S, Demirpence E, Akbiyik F, Solaroglu I, Kilinc A.

Department of Neurosurgery, Spinal Research Laboratory, Hacettepe University Institute of Neurological Sciences and Psychiatry, Ankara Numune Education and Research Hospital; Spinal Research Laboratory, Department of Neurosurgery, Hacettepe University Institute of Neurological Sciences and Psychiatry, Faculty of Medicine, Hacettepe University; Department of Biochemistry, Faculty of Medicine, Hacettepe University; Department of Neurosurgery, Ankara Numune Education and Research Hospital, Sihhiye, Ankara, Turkey.

Melatonin, a product of the pineal gland, is an effective free-radical scavenger both in vitro and in vivo. Free-radical-mediated lipid peroxidation has been increasingly considered as an important factor in post-traumatic neuronal degeneration. The aim of the present study was (i) to examine the responses of different regions of central nervous system (CNS) to free-radical generation induced in vitro and (ii) to test the efficacy of melatonin in reducing oxidative damage in different regions of the CNS. Rat brain, total spinal cord, spinal cord white matter and optic nerves were dissected with the rats under general anesthesia and immediately frozen at -20 degrees C. Thiobarbituric acid reactive substances were measured as an index of lipid peroxidation. Peroxidation was induced with ferrous iron (0.02 mm), ascorbate (1 mm), and hydrogen peroxide (H2O2) (0.5 mm). All tissue samples showed increased lipid peroxidation levels after treatment with free-radical generating agents. The highest amount of damage was observed in the presence of ferrous iron, ascorbate, and H2O2. Melatonin showed antioxidant effects in the brain, total spinal cord, optic nerve, and spinal cord white matter. The results show that melatonin has differential protective effects on CNS tissues in vitro and the most potent effect is observed in the spinal cord white matter.

PMID: 12485369 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485368&dopt=Abstract

J Pineal Res 2003 Jan;34(1):26-31

Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6-hydroxymelatonin sulfate.

Griefahn B, Brode P, Blaszkewicz M, Remer T.

Institute for Occupational Physiology, University of Dortmund; Research Institute of Child Nutrition Dortmund, Dortmund, Federal Republic of Germany.

Cross-sectional data on urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion in children suggest a constant melatonin secretion during growth. The present longitudinal study concerned, accordingly, the intra-individual stability of melatonin production during childhood and adolescence. Urine samples collected during a longitudinal investigation of healthy white children and adolescents were analyzed. Forty-six boys and 38 girls were chosen for the present study. They had passed 3-15 annual examinations between their 3rd and 18th yr of age. Each examination included the collection of urine over 24 hr. The daily urinary output of 6-OHMS of the overall 621 samples was quantified by enzyme-linked immunosorbent assay. The analyses clearly revealed for the first time that, despite huge inter-individual differences, melatonin production remains constant in one and the same individual during childhood and adolescence. Additionally, neither a significant sex difference was observed nor was the 6-OHMS output affected by season. The dramatic decrease of plasma melatonin levels as described in the literature is mainly related to an increase in body size rather than to decreasing pineal secretion.

PMID: 12485368 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485371&dopt=Abstract

J Pineal Res 2003 Jan;34(1):40-52

Protective effect of melatonin and its precursor L-tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion.


Jaworek J, Leja-Szpak A, Bonior J, Nawrot K, Tomaszewska R, Stachura J, Sendur R, Pawlik W, Brzozowski T, Konturek SJ.

Chair of Physiology, Jagiellonian University CM, Krakow, Poland.

Melatonin, a pineal secretory product, synthesized from l-tryptophan, has received increased attention because of its antioxidative and immunomodulatory properties. It has been detected in the gut and shown to protect the gastric mucosa, and liver from acute damage, but the role of melatonin in the protection of the pancreas against acute inflammation is not clear. The aim of this study was to investigate the effects of melatonin and its precursor, l-tryptophan, on caerulein-induced pancreatitis (CIP) and on ischemia/reperfusion (I/R)-provoked pancreatitis in rats. CIP was induced by subcutaneous infusion of caerulein to the rats (25 &mgr;g/kg). I/R was induced by clamping of the inferior splenic artery for 30 min followed by 2 hr of reperfusion. Melatonin (10, 25 or 50 mg/hr) or l-tryptophan (50, 100 or 250 mg/kg) was given as a bolus intraperitoneal (i.p.) injection 30 min prior to the onset of pancreatitis. CIP and I/R were confirmed by histologic examination and manifested by typical pancreatic edema, by an increase of plasma levels of amylase (by 500% in CIP and by 40% in I/R) and the pro-inflammatory tumor necrosis factor alpha (TNFalpha) (by 500%). Lipid peroxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), were increased several fold in the pancreas CIP and I/R, whereas pancreatic blood flow (PBF) was significantly reduced in these animals. Pretreatment of rats subjected to CIP or to I/R with melatonin (25 or 50 mg/kg i.p.) or l-tryptophan (100 or 250 mg/kg i.p.) significantly reduced pancreatic edema, plasma levels of amylase and TNFalpha and diminished pancreatic MDA + 4-HNE contents, while enhancing PBF, pancreatic integrity and plasma levels of the anti-inflammatory interleukin 10 (IL-10). This was accompanied by a marked and dose-dependent rise of plasma melatonin immunoreactivity. Gene expression of N-acetyl transferase, an enzyme involved in melatonin biosynthesis, was detected in the pancreas of normal rats and was significantly enhanced in the rats with CIP. We conclude that exogenous melatonin, and that produced from l-tryptophan, attenuates pancreatic damage induced by CIP or by I/R and this effect may be attributable to the reduction in lipid peroxidation and TNFalpha release combined with an increase of plasma anti-inflammatory IL-10 in rats with acute pancreatitis.

PMID: 12485371 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485373&dopt=Abstract

J Pineal Res 2003 Jan;34(1):60-8
Effects of continuous light exposure on antioxidant enzymes, porphyric enzymes and cellular damage in the Harderian gland of the Syrian hamster.

Tomas-Zapico C, Coto-Montes A, Martinez-Fraga J, Rodriguez-Colunga MJ, Tolivia D.

Departamento de Morfologia y Biologia Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.

The Syrian hamster Harderian gland (HG), an organ present in the male two secretory cell types (type-I and type-II cells), is physiologically exposed to high oxidative stress because of high concentrations of porphyrins and their precursor, 5-aminolevulinic acid. Because of its juxtaorbital location, the HG is accessible to light, and subject to phototoxic effects of these substances. After having previously demonstrated circadian rhythms in antioxidant enzymes, porphyric enzymes and oxidative damage of proteins and lipids, as well as influences of melatonin on these parameters, we have now studied the effects of continuous light (LL), which suppresses melatonin secretion by the pineal gland. Measurements were performed in two different circadian phases, in order to detect the presence or absence of day/night differences. In LL, no differences between circadian phases of subjective day and subjective night were demonstrable for 5-aminolevulinate synthase, 5-aminolevulinate dehydratase, porphobilinogen deaminase, or superoxide dismutase; temporal differences in glutathione reductase and catalase were markedly diminished, whereas all these parameters showed marked day/night differences in the rats exposed to a light/dark cycle of 14:10. In LL, oxidative damage to lipids was minimally effected, while protein damage was enhanced. LL also caused a reduction in the percentage of type-II cells. Therefore, cell differentiation in the HG does not seem to be controlled only by the androgen, but, unexpectedly, also by melatonin.

PMID: 12485373 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12450773&dopt=Abstract

Med Hypotheses 2003 Jan;60(1):102-3

The puzzle of where cerebrospinal fluid is absorbed: new pieces.

Maurizi CP.

Houston Medical Center, GA, Warner Robins, USA

The widely held theory of cerebrospinal fluid (CSF) absorption by the arachnoid villus system cannot explain the movement of substances within the fluid, the deposition pattern of corpora amylacea on the surface of the brain, and pathological findings in neurological disorders. Experiments studying the movement of melatonin and inulin in the CSF compartment demonstrate that some CSF recycles into the ventricular system and CSF contacting tissue diffusely absorbs some. Photomicrographs of a suprapineal recess portal into the third ventricle are presented. A cycling theory of CSF assigns function to the structure of the choroid fissures and the suprapineal recess.

PMID: 12450773 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12823613&dopt=Abstract

J Pineal Res. 2003 Aug;35(1):45-53.

Regional heterogeneity in immunoreactive macrophages/microglia in the rat pineal gland.

Jiang-Shieh YF, Wu CH, Chang ML, Shieh JY, Wen CY.

Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan Taiwan; Department and Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Using specific macrophage antibodies (OX-42, OX-6, ED-1 and ED-2), this study examined the distribution of macrophages/microglia in the pineal gland of adult rats. Except for ED-2, all antibodies labeled distinct subpopulations of macrophages/microglia in the gland; ED-2 labeling was hardly detectable. The quantitative study showed that the pineal macrophages/microglia (PMM) expressing complement type 3 receptors (OX-42) were more numerous than those expressing the major histocompatibility complex class II antigen (OX-6) or unknown cytoplasmic/lysosomal antigens (ED-1). The PMM were ubiquitous, especially the OX-42 labeled cells which were distributed from the dorsal to the ventral aspect of the gland. The macrophages/microglia labeled with OX-6 or ED-1 were localized mainly in the intermediate portion of the pineal gland. Immunolabeled cells were sparsely distributed in the distal portion of the pineal gland. A notable feature was that the OX-6 labeled macrophages/microglia showed a proximal-distal gradient in cell density. Another interesting feature was the occurrence of prominent cell aggregations around the larger blood vessels. These cells were mostly round and exhibited different immunoreactivity. Confocal microscopic study with triple immunolabeling further revealed that individual PMM cell possessed two or more different antigens (ED-1+/OX-6+, OX-42+/OX-6+ or OX-42+/ED-1+). Remarkably, a large population co-expressed ED-1+/OX-6+/OX-42+. The present results show that the expression of immunoreactive molecules in PMM varies in topographical distribution of the cells. It is suggested that this may be linked to their immunoregulatory functions in the gland.

PMID: 12823613 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485375&dopt=Abstract

J Pineal Res 2003 Jan;34(1):75-8

Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin.

Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, Reiter RJ.

Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Institute of Zoology and Anthropology, University of Gottingen, Gottingen, Germany.

Melatonin, a derivative of an essential amino acid, tryptophan, was first identified in bovine pineal tissue and subsequently it has been portrayed exclusively as a hormone. Recently accumulated evidence has challenged this concept. Melatonin is present in the earliest life forms and is found in all organisms including bacteria, algae, fungi, plants, insects, and vertebrates including humans. Several characteristics of melatonin distinguish it from a classic hormone such as its direct, non-receptor-mediated free radical scavenging activity. As melatonin is also ingested in foodstuffs such as vegetables, fruits, rice, wheat and herbal medicines, from the nutritional point of view, melatonin can also be classified as a vitamin. It seems likely that melatonin initially evolved as an antioxidant, becoming a vitamin in the food chain, and in multicellular organisms, where it is produced, it has acquired autocoid, paracoid and hormonal properties.

PMID: 12485375 [PubMed - in process]

Note from FAN; Definitions:
Autocoid - a chemical substance produced by one type of cell that affects the function of different types of cells in the same region, thus functioning as a local hormone or messenger. [G. autos, self, + eidos, form]
Paracoid - not listed.
Ref: Stedman's Concise Medical Dictionary for the Health Professions. 2001.. Illustrated 4th Edition. Ed. John H. Dirckx, MD. Lippincott Williams & Wilkins, Baltimore, Maryland.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12825223&dopt=Abstract

Med Pediatr Oncol. 2003 Aug;41(2):151-3.
No Abstract available

Pineal dysfunction (low melatonin production) as a cause of sudden death in a long-term survivor of langerhans cell histiocytosis?

Imashuku S, Morimoto Y, Morimoto A, Yamamoto T, Hibi S, Todo S.

Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan.

PMID: 12825223 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12834439&dopt=Abstract

J Neuroendocrinol. 2003 Aug;15(8):778-86.

MT1 Melatonin Receptor mRNA Expressing Cells in the Pars Tuberalis of the European Hamster: Effect of Photoperiod.

Dardente H, Klosen P, Pevet P, Masson-Pevet M.
Neurobiologie des Rythmes, UMR 7518 CNRS/ULP, Strasbourg, France.

Melatonin, secreted only during the night by the pineal gland, transduces the photoperiodic message to the organism. One important target for the hormone is the pars tuberalis (PT) of the adenohypophysis which displays a very high number of melatonin binding sites in mammals and is implicated in the seasonal regulation of prolactin secretion. To gain insight into the mechanism by which the melatonin signal is decoded in the PT, we studied the effect of photoperiod on the PT cells expressing the MT1 melatonin receptor in a highly photoperiodic species, the European hamster. Recently, we showed that, in the rat, the MT1 receptor mRNA is expressed in PT-specific cells characterized by their expression of beta-thyroid stimulating hormone (beta-TSH) along with the alpha-glycoprotein subunit (alpha-GSU). As the cellular composition of the PT shows variability among species, we first identified the cell type expressing the MT1 receptor in the European hamster by combining immunocytochemistry and nonradioactive in situ hybridization for the MT1 receptor mRNA. Our results show that, in the European hamster, as in the rat, the MT1 receptor is only expressed by the PT-specific-cells, beta-TSH and alpha-GSU positive. In a second step, we analysed the effects of photoperiod on the MT1 mRNA, and on beta-TSH and alpha-GSU both at the mRNA and protein levels. Our data show that, compared to long photoperiod, short photoperiod induces a dramatic decrease of MT1, beta-TSH and alpha-GSU expression. Protein levels of beta-TSH and alpha-GSU were also dramatically reduced in short photoperiod. Together, our data suggest that melatonin exerts its seasonal effects in the PT by signalling to PT specific-cells through the MT1 receptor subtype.
PMID: 12834439 [PubMed - in process]