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Pineal Gland Abstracts: 2002

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

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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12596522&dopt=Abstract

Eksp Klin Farmakol. 2002 Sep-Oct;65(5):73-80.

[Immunotropic properties of pineal melatonin]

[Article in Russian]

Arushanian EB, Beier EV.

Pharmacology Department, Stavropol State Medical Academy, ul. Mira 310, Stavropol, 355024 Russia.

An analysis of the presently available data shows that the principal pineal hormone melatonin is capable of influencing, both directly and indirectly, the state of the immune system. The immunotropic activity of this hormone can account for the stress-protective, antitumor, and antiviral effects of melatonin.

Publication Types: Review Review, Tutorial

PMID: 12596522 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11899099&dopt=Abstract

Curr Top Med Chem. 2002 Feb;2(2):167-79.

Melatonin-immune system relationships.

Guerrero JM, Reiter RJ.

Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine and Virgen Macarena Hospital, Spain. guerrero@cica.es

In this paper we review the historical milestones that first highlighted the existence of a relationship between melatonin and the immune system and we summarize data from experiments which correlate the rhythmic production of melatonin with the rhythmic activity of the immune system. The effects of pinealectomy and in vivo administration of melatonin on a variety of immune parameters, including specific and non-specific immunity are considered and we also present contradictory data concerning the effect of melatonin in cultured immunocompetent cells and a possible scheme of how melatonin regulates the production of a number of cytokines. Finally, the mechanism of action of melatonin in the immune system is discussed. Many data suggest the existence of both nuclear and membrane receptors for melatonin in the immune system. Both of these appear to be clearly identified but their specific physiological role is still under discussion. In summary, although there is overwhelming information demonstrating the immunoenhancing properties of melatonin, many questions related to the cytokines involved and the mechanisms of action of the indoleamine require answers.

Publication Types: Review; Review, Tutorial

PMID: 11899099 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15457683

Stud Health Technol Inform. 2002;91:1-6.

The effects of exposure to intense, 24 h light on the development of scoliosis in young chickens.

Nette F, Dolynchuk K, Wang X, Daniel A, Demianczuk C, Moreau M, Raso J, Mahood J, Bagnall K.

Division of Anatomy, University of Alberta, Edmonton, Alberta, Canada. T6G 2H7.

The aetiology of adolescent 5 coliosis remains unknown and hindering research is the absence of an appropriate animal model. It is now well-established that pinealectomy in young chickens results in the development of scoliosis that has many of the characteristics seen in patients with adolescent idiopathic scoliosis but the mechanism underlying this phenomenon remains elusive. The principle product of the pineal gland is melatonin and so many studies have focused on studying the effects of reduced levels of this hormone. The results have been mixed and the role of melatonin remains unclear. As melatonin production is inhibited by light, it was hypothesised that providing the chickens with an environment consisting of intense, continuous light would reduce serum melatonin levels and avoid any of the potential artifacts involved with the pinealectomy surgery. Consequently, pinealectomised and normal chickens were exposed to very intense light for complete 24 h in each day. At the end of 22 days in this environment serum melatonin levels had been reduced to very low levels in all chickens. Most importantly, 15% of the normal chickens had developed scoliosis and the number of pinealectomised chickens that developed scoliosis increased from 50% to 80%. The results showed that a method for reducing serum melatonin without pinealectomy has been established and which can be used in further experiments. Furthermore, the results also showed that reduced levels of serum melatonin has significant effects on the development of scoliosis. The indication is that there is a threshold level of serum melatonin below which scoliosis may develop probably in conjunction with some other factor which has yet to be identified.

PMID: 15457683 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15455995

Stud Health Technol Inform. 2002;88:3-9.

The development of scoliosis following pinealectomy in young chickens is not the result of an artifact of the surgical procedure.

Bagnall K, Raso J, Moreau M, Mahood J, Wang X, Beuerlein M.

Department of Surgery, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. kbagnall@med.ualberta.ca

Pinealectomy in young chickens consistently results in scoliosis which has many characteristics similar to those seen in adolescent idiopathic scoliosis. The mechanism underlying this phenomenon remains a mystery and it is not yet entirely clear whether some unidentified aspect of the extensive surgery is the major factor rather than the removal of the pineal gland. Four different types of pinealectomy surgery were performed on young chickens as well as deliberate damage to the cerebral cortex which simulated the extreme of any accidental damage that might occur during surgery. Scoliosis was assessed from weekly radiographs. No differences in incidence of scoliosis, degree of severity or pattern of curve development were observed for any of the experimental groups when compared with controls. In all groups approximately 55% of the chickens developed scoliosis that progressed rapidly. Different pinealectomy procedures and deliberate damage to the cerebral cortex produce scoliosis in young chickens with the same incidence and characteristics. This suggests strongly that the mechanism behind the phenomenon is due to the removal of the pineal gland and not some artifact of the extensive surgery. The pinealectomy model in young chickens is proving to be a good model for studying AIS in humans. An understanding of the mechanism underlying this phenomenon has the potential to provide further insights into the aetiology of AIS and can lead to the development of novel treatement methods.

PMID: 15455995 [PubMed - in process]

 

From Toxnet

Source: Govt Reports Announcements & Index (GRA&I), Issue 09, 2003

Melatonin, Aging and Breast Cancer.

Hill SM

Tulane Univ., New Orleans, LA.

Abstract: Annual rept. 1 Jun 2001-31 May 2002.

Order Number: 12p 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.

Price: NTIS Prices: PC A03/MF A01 Entry Month: March, 2003

Year of Publication: 2002

Secondary Source ID: NTIS/ADA408705

Note previous report published in 2001:

Melatonin, Aging and Breast Cancer.

Hill SM

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

Source: Govt Reports Announcements & Index (GRA&I), Issue 06, 2002

Abstract: Annual rept. 1 Jun 2000-31 May 2001. An increasing percentage of elderly women, particularly in industrialized countries, are developing breast cancer. Numerous hypotheses have been proposed to explain this dramatic increase in breast cancer incidence in the later stages of life. However, an alternative hypothesis is that aging results in changes in the internal milieu of the organism, such as metabolic, endocrine and immunologic shifts, providing increasingly favorable conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer. As individuals age, there is the onset of disrupted sleep leading to a significant suppression in the nocturnal levels of melatonin after age 60. Using the Buffalo rat as a model, we have begun to characterize the melatonin rhythm in young vs. aged female rats.

Order Number: 10p 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.

Price: NTIS Prices: PC A02/MF A01


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12111545&dopt=Abstract

Cell Tissue Res 2002 Jul;309(1):151-62
 
Mammalian melatonin receptors: molecular biology and signal transduction.

von Gall C, Stehle JH, Weaver DR.

Department of Neurobiology, University of Massachusetts Medical School, Worcester, 01605, USA.

The pineal hormone, melatonin, is an important regulator of seasonal reproduction and circadian rhythms. Its effects are mediated via high-affinity melatonin receptors, located on cells of the pituitary pars tuberalis (PT) and suprachiasmatic nucleus (SCN), respectively. Two subtypes of mammalian melatonin receptors have been cloned and characterized, the MT1 (Mel(1a)) and the MT2 (Mel(1b)) melatonin receptor subtypes. Both subtypes are members of the seven-transmembrane G protein-coupled receptor family. By using recombinant melatonin receptors it has been shown that the MT1 melatonin receptor is coupled to different G proteins that mediate adenylyl cyclase inhibition and phospholipase C beta activation. The MT2 receptor is also coupled to inhibition of adenylyl cyclase and additionally it inhibits the soluble guanylyl cyclase pathway. In mice with a targeted deletion of the MT1 receptor, the acute inhibitory effects of melatonin on SCN multiunit activity are completely abolished, while the phase-shifting responses to melatonin (given in physiological concentrations) appear normal. Furthermore, melatonin inhibits the phosphorylation of the transcription factor cyclic AMP response element binding protein, induced by the pituitary adenylate cyclase-activating polypeptide in SCN cells predominantly via the MT1 receptor. However, a functional MT2 receptor in the rodent SCN is partially able to compensate for the absence of the MT1 receptor in MT1 receptor-deficient mice. These findings indicate redundant and non-redundant roles of the receptor subtypes in regulating SCN function. In the PT, a functional MT1 receptor is essential for the rhythmic synthesis of the clock gene product mPER1. Melatonin produces a long-lasting sensitization of adenylyl cyclase and thus amplifies cyclic AMP signaling when melatonin levels decline at dawn. This action of melatonin amplifies gene expression rhythms in the PT and provides a mechanism for reinforcing rhythmicity in peripheral tissues which themselves lack the capacity for self-sustained oscillation. Mice with targeted deletion of melatonin receptor subtypes provide an excellent model to understand cellular mechanisms through which melatonin modulates circadian and photoperiodic rhythmicity.

Publication Types:

  • Review
  • Review Literature

PMID: 12111545 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12812036&dopt=Abstract

An R Acad Nac Med (Madr). 2002;119(3):463-77.

[In Process Citation]

[Article in Spanish]

Munoz Barragan L.

The pineal gland is an epithalamic structure whose mission is to integrate incoming environmental information with other types of information deriving from the inner milieu itself of the organism, releasing melatonin, a substance able to elicit responses in the central nervous and endocrine systems. Secreted rhythmically during the scotophase, melatonin is involved in reproductive mechanisms, in cyclically developing nosological processes, and in the genesis or maintenance of cerebral biorhythms. Owing to its ability to uptake free radicals produced by cell metabolism, it is a potent antioxidant agent that is able to delay cellular ageing and inhibit cellular proliferation in both experimental and spontaneous tumours.

PMID: 12812036 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12489344&dopt=Abstract

Ann Anat 2002 Nov;184(6):583-93

[Article in German]

Vollrath L.

Anatomisches Institut der Johannes Gutenberg-Universitat, Becherweg 13, D-55099 Mainz, Deutschland. vollrath@mail.uni-mainz.de

The present review deals with important new chronobiological results especially in the field of chronoendocrinology, shedding new light on the circadian organisation of mammals including man. In vitro studies have shown that the concept of the existence of a single circadian oscillator located in the suprachiasmatic nucleus has to be extended. Circadian oscillators have also been found to exist in the retina, islets of Langerhans, liver, lung, and fibroblasts. Another major result is the detection of a new photopigment, melanopsin, present in a subpopulation of retinal ganglion cells which are lightsensitive and project to the suprachiasmatic nucleus, acting as zeitgeber for the photic entrainment of the circadian rhythm. We are only beginning to understand how the circadian oscillator transmits the circadian message to the endocrine system. The generation of circadian and seasonal rhythms of hormone synthesis is best understood in the pineal gland and its hormone melatonin. Seasonal changes of melatonin synthesis are transduced in the pars tuberalis of the adenohypophysis which is now entering the limelight of chronoendocrinological research. Currently, the elucidation of the genetic basis and the molecular organisation of the circadian oscillator within individual cells is a major thrust in chronobiological research.

PMID: 12489344 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12500169&dopt=Abstract

Neuroendocrinol Lett 2002 Oct-Dec;23(5-6):443-6

Effect of superior cervical ganglionectomy on the ultrastructure of pinealocytes in the Djungarian hamster (Phodopus sungorus): Quantitative study.


Karasek M, Zielinska A, Marek K, Swietoslawski J.

Department of Electron Microscopy, Chair of Pathomorphology, Medical University of Lodz, Lodz, POLAND.

OBJECTIVES: Superior cervical ganglia are of crucial importance in regulating the secretion of the pineal hormone melatonin. Changes in pineal morphology have been observed in many mammalian species after sympathectomy. Therefore, we decided to investigate the ultrastructure of Djungarian hamster pinealocytes following superior cervical ganglionectomy.
MATERIAL AND METHODS: Eight adult female Djungarian hamsters (Phodopus sungorus) were used in this study. The superior cervical ganglia were removed bilaterally in four animals, whereas the other four animals served as sham-operated controls. The pineal glands were removed four weeks after the operation and processed for electron microscopic study. The cross-sectional areas of pinealocyte and its nucleus, and relative volume of mitochondria, Golgi apparatus, lysosomes, granular endoplasmic reticulum, and glycogen particles as well as the numbers of dense-core vesicles and "synaptic" ribbons were estimated using a digital analyzer connected on-line to IBM-PC computer. Statistical analysis of the data was performed using Student's t test and Snedecor F test.
RESULTS: Significant reduction in the cross-sectional areas of the pinealocyte and its nucleus as well as in the relative volumes of mitochondria and glycogen particles was observed after superior cervical ganglionectomy in comparison with sham-operated controls. Sympathectomy resulted also in reduction of the number of dense-core vesicles. On the contrary 2,5 fold increase in the number of "synaptic" ribbons was observed in ganglionectomized animals in comparison to sham-operated controls.
CONCLUSION: Deprivation of sympathetic innervation leads in Djungarian hamsters not only to suppression of melatonin synthesis and secretions but, as appears from our studies, induces also morphological changes suggesting lower metabolic and secretory activity of pinealocytes.

PMID: 12500169 [PubMed - in process]
FAN note: Definition: Sympathectomy is a surgical procedure that destroys nerves in the sympathetic nervous system. The procedure is done to increase blood flow and decrease long-term pain in certain diseases that cause narrowed blood vessels. It can also be used to decrease excessive sweating. This surgical procedure cuts or destroys the sympathetic ganglia, collections of nerve cell bodies in clusters along the thoracic or lumbar spinal cord. - ref: http://www.ehendrick.org/healthy/00067130.html

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12084526&dopt=Abstract

Peptides 2002 May;23(5):941-5

Age differences in neurokinin A and substance P from the hypothalamus, pituitary, pineal gland, and striatum of the rat. Effect of exogenous melatonin.

Fernandez C, Debeljuk L, Diaz E, Diaz B.

Dpto. de Biologia Funcional, Area Fisiologia, Facultad de Medicina, Universidad de Oviedo, 33006, Oviedo, Spain

Previous data showed that aging of the central nervous system (CNS) is associated with widespread changes in tachykinin gene expression. However, there are no data about the possible role of exogenous melatonin in modulating the tachykinergic system during aging. The aim of this work was to analyze the age-dependent changes on neurokinin A (NKA) and substance P (SP) levels in hypothalamus, pituitary, pineal gland and striatum and the role of exogenous melatonin on these changes. We studied female rats at three different ages: 5-month-old (cyclic), 15-month-old (preacyclic) and 25-month-old (acyclic). Hypothalamic tachykinin levels increase when female rats reached acyclicity, this increase was blunted in acyclic-melatonin-treated rats. However, melatonin treatment in young cyclic rats resulted in significantly increased values as compared to controls. Pituitary NKA concentrations did no show age-dependent changes in control rats, however, in both, preacyclic and acyclic-melatonin-treated rats significantly increased values of pituitary NKA were found compared to controls. In the pineal gland, a marked decrease of NKA levels was observed in acyclic-control rats. Melatonin treatment did not alter this decrease. In the striatum, NKA and SP concentrations were significantly reduced in preacyclic- and acyclic-control rats compared to young cyclic rats, melatonin had no effect on striatal tachykinins. Our results indicate that melatonin may regulate tachykinin stores during aging mainly on structures of the neuroendocrine-reproductive axis.

PMID: 12084526 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12500168&dopt=Abstract

Neuroendocrinol Lett 2002 Oct-Dec;23(5-6):442

Book Review:

Csilla Ruzsas and Bela Mess "Maturation and Aging of Neuroendocrine Functions. The role of monoaminergic neurons and of the pineal gland".

Dorner G.

Institute of Experimental Endocrinology, Humboldt University Medical School (Charite), Berlin, Germany.

Publication Types:

PMID: 12500168 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12408559&dopt=Abstract

Anal Quant Cytol Histol 2002 Oct;24(5):263-79

Pathobiology of testicular germ cell tumors: views and news.


Looijenga LH, Oosterhuis JW.

Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, The Netherlands. looijenga@leph.azr.nl

Human germ cell tumors (GCTs) are a heterogeneous group of neoplasms. They can occur in different anatomic locations, predominantly in the gonads (both ovary and testis) and in the midline of the body, including the retroperitoneal, mediastinal and hypothalamus/pineal gland regions. This distribution has been related to the migration routefollowed by primordial germ cells from the yolk sac to the genital ridge. The clinical behavior of these tumors depends on the sex of the patient, the age at clinical presentation and the histology of the tumor, Within the testis, three groups of GCTs can be distinguished; (I) yolk sac tumors and teratomas of neonates and infants; (II) seminomas and nonseminomas of adolescents and adults, the so-called testicular germ cell tumors; and (III) spermatocytic seminomas. This review discusses the histology, epidemiology and chromosomal constitution of GCT, in particular of the seminomas and nonseminomas of the adult testis, including their precursor, carcinoma in situ. In addition, the available data on the molecular basis of treatment sensitivity and resistance of GCT are reviewed.

PMID: 12408559 [PubMed - in process]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12019354&dopt=Abstract
Neuroendocrinol Lett 2002 Apr;23 Suppl 1:61-6
Melatonin in immunity: comparative aspects.

Skwarlo-Sonta K.

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

Pineal gland, by the diurnal rhythm of synthesis and release of its principal hormone, melatonin (MEL), is involved in reciprocal relationships between neuroendocrine and immune systems, responsible for keeping internal homeostasis in vertebrate animals. In this paper the experimental data, indicating that both strategic (developmental, thus antigen independent) and emergency (evoked by antigenic activation of the mature immune system) levels of interactions between pineal gland and immune system, operate in mammals and birds, are reviewed. The cells and organs of immune system using membrane receptors as well as nuclear orphan receptors perceive MEL message. Effects exerted by MEL on immune parameters are different, and depend on several factors, including dose and way of MEL application, species, sex, age of animal, its immune system maturation, way of immune system activation, and parameter examined, as well as the season, circadian rhythm of both immunity and pineal gland function, stressful conditions, accompanying experimental procedure, etc. In turn, lymphoid organ-derived hormones and cytokines, soluble factors secreted by activated immune cells act as messages understood by the pineal gland, closing the regulatory loop of the bi-directional functional connections between both systems.

Publication Types:

PMID: 12019354 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12445135&dopt=Abstract

Pathol Int 2002 Oct;52(10):636-642

Identification of an aging-related spherical inclusion in the human brain.

Kimura T, Fujise N, Ono T, Shono M, Yuzuriha T, Katsuragi S, Takamatsu J, Miyakawa T, Kitamura T.

Department of Psychiatry, Kumamoto University School of Medicine, Saga, Japan National Kikuchi Keifuen Hospital, Saga, Japan Division of Clinical Research, National Kikuchi Hospital, Saga, Japan Labor Welfare Corporation Kumamoto Rosai Hospital, Kumamoto, Saga, Japan Center for Emotional and Behavioral Disorders, Hizen National Mental Hospital, Saga, Japan.

Inclusions, such as corpora amylacea, axonal spheroids and ubiquitin-positive granular structures, are present in aged brains. We found a phosphorylated tau-positive inclusion in brain tissues obtained from 13 non-demented subjects and five patients with Alzheimer's disease. This inclusion was spherical and 3-20 micro m in size. It was most frequently detected in the hippocampal CA1 region and in the prosubiculum but was not present in the white matter. The density of this inclusion increased significantly with aging and decreased after the occurrence of neurofibrillary tangles. The presence of the inclusion was confirmed using immunoelectron microscopy. These findings show a possibility that the inclusion is a novel aging-related structure in the human brain.

PMID: 12445135 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12387519&dopt=Abstract

J Pediatr Endocrinol Metab 2002 Sep-Oct;15(8):1195-201

hCG-secreting pineal teratoma causing precocious puberty: report of two patients and review of the literature.

Nogueira K, Liberman B, Pimentel-Filho FR, Goldman J, Silva ME, Vieira JO, Buratini JA, Cukiert A.

Department of Endocrinology, Hospital Brigadeiro, Sao Paulo SP, Brazil.

Two boys are described with precocious puberty (PP) due to pineal immature teratoma associated with choriocarcinoma. Patient 1 was a 7 year-old boy with a 2-year history of PP. He had elevated CSF and plasma beta-hCG levels. Magnetic resonance imaging (MRI) showed a 3.0 cm pineal mass. He was initially submitted to a trial with radiotherapy, followed by radical surgical resection, stereotactic radiotherapy and chemotherapy. Long-term follow up included the appearance of acute hydrocephalus requiring CSF shunting, local hemorrhage and extensive radionecrosis. Death occurred 1.5 years after diagnosis. Patient 2 was a 7 year-old boy with an 8-month history of PP. He had elevated CSF and plasma beta-hCG and alpha-fetoprotein levels. MRI showed a 1.0 cm pineal mass. He was submitted to radical surgical resection (which caused normalization of levels of markers) and prophylactic chemotherapy. The boy is doing well 1.5 years after diagnosis. An extensive review of the literature corroborates the idea that this last treatment paradigm (surgery and chemotherapy) probably represents the best treatment regimen for these patients.

PMID: 12387519 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11961500&dopt=Abstract

Minerva Endocrinol 2002 Jun;27(2):73-7

[Melatonin/circadian rhythm. Is there a feedback between epiphysis and hypophysis?]

[Article in Italian]

Pallotti S, Nordio M, Giuliano S.

Dipartimento di Fisiopatologia Medica, Policlinico Umberto I, Universita degli Studi di Roma La Sapienza, Rome, Italy.

BACKGROUND: The study evaluates the circadian rhythm of melatonin in relation to sex and age and identified contemporary alterations in the secreton of some hypophyseal hormones, suggesting that melatonin may exert a modulatory action on the latter.
METHODS: The melatonin metabolite (6-hydroxymelatonin sulfate) was assayed in urine samples from 48 subjects of both sexes aged between 25 and 60 years old using the RIA method described by Arendt, modified for the ise of iodine markers. A blood sample was taken from the same subjects to assay hypophyseal hormones.
RESULTS: Melatonin secretion does not remain constant over 24 hours in young subjects of both sexes, but instead is rhythmic. This rhythmic secretion is lacking in adults, revealing a daytime pineal secreton that is surprisingly higher than in younger persons. A difference in secretion levels was also found between sexes, a higher melatonin peak in females compared to males. Some young female subjects reveal a contemporary hypersecretion of the somatotropic hormone in line with the falling nocturnal peak of melatonin. Subjects with latent hypothyroidism show a diminished melatonin peak compared to that in euthyroid subjects.
CONCLUSIONS: Changes in pineal secretion between the second and sixth decade of life are characterised by the loss of rhythmic secretion, linked not only to the loss of the nocturnal peak but an increased daytime secretion compared to younger subjects. The other finding that emerged from this study was the difference in secretion levels between the sexes. Lastly, we affirm that the pineal gland may exert a modulating influence on the hypophysis.

PMID: 11961500 [PubMed - indexed for MEDLINE]

Note from FAN: Defintion for hypophysis
--
an unpaired compound gland suspended from the base of the hypothalamus by a short extension of the infundibulum, the infundibular or pituitary stalk. The hypophysis consists of two major subdivisions:
1) the neurohypophysis, comprising the infundibulum and its bulbous termination, the neural part or infundibular process (posterior lobe), which is composed of neuroglia-like pituicytes, blood vessels, and unmyelinated nerve fibers of the hypothalamohypophyseal tract whose cell bodies reside in the supraoptic and paraventricular nuclei of the hypothalamus, and convey to the lobe for storage and release the neurosecretory hormones oxytocin and antidiuretic hormone;
2) the adenohypophysis, comprising the larger distal part, a sleevelike extension of this lobe (infundibular part) which invests the infundibular stalk, and a thin intermediate part (poorly developed in humans) between the anterior and posterior lobes; the anterior lobe consists of cords of cells of several different types interspersed with capillaries of the hypothalamohypopysial portal system; secretion of somatotropins, prolactin, thyroid-stimulating hormone, gonadotropins, adrenal corticotropin, and other related peptides in the adenohypophysis is regulated by releasing and inhibiting factors elaborated by neurons in the hypothalamus which are taken up by the primary plexus of capillaries in the mediam eminence and transported via portal vessels in the infundibular part and infundibular stem to a secondary plexus of capillaries in the distal part. SEE ALSO hypothalamus. SYN pituitary gland. [G. an undergrowth]

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=12224052&dopt=Abstract

Bioelectromagnetics 2002 Oct;23(7):488-495

Calcite microcrystals in the pineal gland of the human brain: First physical and chemical studies.

Baconnier S, Lang SB, Polomska M, Hilczer B, Berkovic G, Meshulam G.


Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.

A new form of biomineralization has been studied in the pineal gland of the human brain. It consists of small crystals that are less than 20 &mgr;m in length and that are completely distinct from the often observed mulberry-type hydroxyapatite concretions. A special procedure was developed for isolation of the crystals from the organic matter in the pineal gland. Cubic, hexagonal, and cylindrical morphologies have been identified using scanning electron microscopy. The crystal edges were sharp whereas their surfaces were very rough. Energy dispersive spectroscopy showed that the crystals contained only the elements calcium, carbon, and oxygen. Selected area electron diffraction and near infrared Raman spectroscopy established that the crystals were calcite. With the exception of the otoconia structure of the inner ear, this is the only known nonpathological occurrence of calcite in the human body. The calcite microcrystals are probably responsible for the previously observed second harmonic generation in pineal tissue sections. The complex texture structure of the microcrystals may lead to crystallographic symmetry breaking and possible piezoelectricity, as is the case with otoconia. It is believed that the presence of two different crystalline compounds in the pineal gland is biologically significant, suggesting two entirely different mechanisms of formation and biological functions. Studies directed toward the elucidation of the formation and functions, and possible nonthermal interaction with external electromagnetic fields are currently in progress. Bioelectromagnetics 23:488-495, 2002. Copyright 2002 Wiley-Liss, Inc.

PMID: 12224052 [PubMed - as supplied by publisher]


We add this abstract to indicate fluoride's affinity to calcite. Fluoride's affinity to hydroxyapatite has been established.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12399694&dopt=Abstract

Caries Res 2002 Sep-Oct;36(5):341-6

Defluoridation of drinking water by boiling with brushite and calcite.

Larsen MJ, Pearce EI.

Royal Dental College, Aarhus, Denmark, Wellington School of Medicine, Wellington, New Zealand.

Existing methods for defluoridating drinking water involve expensive high technology or are slow, inefficient and/or unhygienic. A new method is now suggested, encompassing brushite and calcite suspension followed by boiling. Our aim was to examine the efficiency of the method and the chemical reactions involved. Brushite, 0.3-0.5 g, and an equal weight of calcite were suspended in 1 litre water containing 5-20 ppm fluoride. The suspensions were boiled in an electric kettle, left to cool and the calcium salts to sediment. Solution ion concentrations were determined and sediments were examined by X-ray diffraction. In distilled water initially containing 5, 10 and 20 ppm fluoride the concentration was reduced to 0.06, 0.4 and 5.9 ppm, respectively. Using Aarhus tap water which contained 2.6 mmol/l calcium the final concentrations were 1.2, 2.5 and 7.7 ppm, respectively, and runs without calcite gave results similar to those with calcite. Without boiling the fluoride concentration remained unaltered, as did the brushite and calcite salts, despite occasional agitation by hand. All solutions were supersaturated with respect to fluorapatite and hydroxyapatite and close to saturation with respect to brushite. Boiling produced well-crystallised apatite and traces of calcite, while boiling of brushite alone left a poorly crystallised apatite. We conclude that boiling a brushite/calcite suspension rapidly converts the two salts to apatite which incorporates fluoride if present in solution, and that this process may be exploited to defluoridate drinking water. Copyright 2002 S. Karger AG, Basel

PMID: 12399694 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12395907&dopt=Abstract

Dig Dis Sci 2002 Oct;47(10):2336-48

Gastrointestinal melatonin: localization, function, and clinical relevance.

Bubenik GA.

Department of Zoology, University of Guelph, Ontario, Canada.

The gastrointestinal tract of vertebrate species is a rich source of extrapineal melatonin. The concentration of melatonin in the gastrointestinal tissues surpasses blood levels by 10-100 times and there is at least 400x more melatonin in the gastrointestinal tract than in the pineal gland. The gastrointestinal tract contributes significantly to circulating concentrations of melatonin, especially during the daytime and melatonin may serve as an endocrine, paracrine, or autocrine hormone influencing the regeneration and function of epithelium, enhancing the immune system of the gut, and reducing the tone of gastrointestinal muscles. As binding sites for melatonin exhibit circadian variation in various species, it has been hypothesized that some melatonin found in the gastrointestinal tract might be of pineal origin. Unlike the photoperiodically regulated production of melatonin in the pineal, the release of gastrointestinal melatonin seems to be related to the periodicity of food intake. Phylogenetically, melatonin and its binding sites were detected in the gastrointestinal tract of lower vertebrates, birds, and mammals. Melatonin was found also in large quantities in the embryonic tissue of the mammalian and avian gastrointestinal tract. Food intake and, paradoxically, also longterm food deprivation resulted in an increase of tissue and plasma concentrations of melatonin. Melatonin release may have a direct effect on many gastrointestinal tissues but may also well influence the digestive tract indirectly, via the central nervous system and the sympathetic and parasympathetic nerves. Melatonin prevents ulcerations of gastrointestinal mucosa by an antioxidant action, reduction of secretion of hydrochloric acid, stimulation of the immune system, fostering epithelial regeneration, and increasing microcirculation. Because of its unique properties, melatonin could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers, irritable bowel syndrome, and childhood colic.

Publication Types:

PMID: 12395907 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12224052&dopt=Abstract

Bioelectromagnetics 2002 Oct;23(7):488-95

Calcite microcrystals in the pineal gland of the human brain: first physical and chemical studies.

Baconnier S, Lang SB, Polomska M, Hilczer B, Berkovic G, Meshulam G.

Department of Chemical Engineering, Ben-Gurion University of the Negev, 84105 Beer Sheva, Israel.

A new form of biomineralization has been studied in the pineal gland of the human brain. It consists of small crystals that are less than 20 microm in length and that are completely distinct from the often observed mulberry-type hydroxyapatite concretions. A special procedure was developed for isolation of the crystals from the organic matter in the pineal gland. Cubic, hexagonal, and cylindrical morphologies have been identified using scanning electron microscopy. The crystal edges were sharp whereas their surfaces were very rough. Energy dispersive spectroscopy showed that the crystals contained only the elements calcium, carbon, and oxygen. Selected area electron diffraction and near infrared Raman spectroscopy established that the crystals were calcite. With the exception of the otoconia structure of the inner ear, this is the only known nonpathological occurrence of calcite in the human body. The calcite microcrystals are probably responsible for the previously observed second harmonic generation in pineal tissue sections. The complex texture structure of the microcrystals may lead to crystallographic symmetry breaking and possible piezoelectricity, as is the case with otoconia. It is believed that the presence of two different crystalline compounds in the pineal gland is biologically significant, suggesting two entirely different mechanisms of formation and biological functions. Studies directed toward the elucidation of the formation and functions, and possible nonthermal interaction with external electromagnetic fields are currently in progress. Copyright 2002 Wiley-Liss, Inc.

PMID: 12224052 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12354131&dopt=Abstract

Clin Endocrinol (Oxf) 2002 Oct;57(4):487-500

Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen.

Janmohamed S, Grossman AB, Metcalfe K, Lowe DG, Wood DF, Chew SL, Monson JP, Besser GM, Plowman PN.

Department of Endocrinology, St. Bartholomew's Hospital, London EC1A 7BE, UK.

OBJECTIVE: Suprasellar germ cell tumours are rare, and there are few series of patients outlining the problems in diagnosis and management, and providing clear guidelines for optimal therapy. We have therefore reviewed our own series of 11 such patients who were managed in a joint endocrinology/clinical oncology setting.
PATIENTS AND DESIGN: A retrospective case review assessment of all patients seen within a given time. Clinical, biochemical and radiological findings were reviewed, the types of therapy administered noted, and the responses to treatment analysed.
RESULTS: In the years 1977-2001, 11 patients with suprasellar (SS) germ cell tumours (GCT) were seen (germinomatous : nongerminomatous = 8 : 3). SSGCT had an approximately equal sex incidence (M : F, 6 : 5), in contrast to pineal tumours, the commonest site of origin of intracranial GCT and which occur predominantly in men. The median age at presentation was 20 years (range 6-49 years) with a median duration of symptoms before diagnosis of 17 months (range 1-35 months). Polyuria was the commonest presenting symptom (10 patients). Diabetes insipidus occurred in all patients, as did partial or complete anterior pituitary failure. Visual failure was present in 55% of cases. Anorexia, weight loss and disturbed thirst sensation were also common. Positron emission tomography scanning was occasionally useful in the evaluation of suprasellar tumours/pituitary stalk lesions deemed too risky to biopsy. A "central nervous system-friendly" chemoradiotherapy regimen comprising vincristine, etoposide and carboplatin and differential daily dose irradiation, usually administered using a partial transmission block technique, produced a 5-year survival of 100% with low morbidity. Treatment did not correct previously abnormal endocrine function although it did improve vision in three of six patients.
CONCLUSIONS: We therefore emphasize the use of techniques other than biopsy in the diagnosis of these patients, note the problems in the management of their fluid control, and highlight the favourable response to a combined chemotherapy-radiotherapy protocol.

PMID: 12354131 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12004644&dopt=Abstract

Arch Ital Biol 2002 Apr;140(2):129-58

Pineal gland hormone and idiopathic scoliosis: possible effect of melatonin on sleep-related postural mechanisms.

Pompeiano O, Manzoni D, Miele F.

Dipartimento di Fisiologia e Biochimica, Universita di Pisa, Via S. Zeno 31, 1-56127 Pisa, Italy. pompeiano@dfb.unipi.it

Experimental and clinical evidences indicate that endocrine mechanisms, particularly involving the pineal gland, exert a role in the development of postural deficits leading to the occurrence of idiopatic scoliosis (IS). In particular, experiments performed in bipedal animals have shown that removal of the pineal gland, which secretes melatonin (M), induced a scoliosis, and that in such preparations, administration of this hormone prevented the development of this deformity (cf. 131). It appears also that adolescents with IS showed a reduced level of serum M with respect to age-related control subjects. The possible mechanisms involved in the M regulation of the tonic contraction of the axial musculature have been discussed. It is known that the pineal gland is implicated in the control of circadian rhythms, including the sleep-waking cycle, and that during this cycle there are prominent changes in postural activity, which affect not only the limbs, but also the axial musculature. These changes are characterized by a decrease followed by a suppression of postural activity, which occur particularly during transition from wakefulness to synchronized sleep and, more prominently, to rapid eye movement (REM) sleep. Episodes of postural atonia may also occur during the cataplectic episodes, which are typical of narcolepsy. Cholinergic and/or cholinoceptive neurons located in the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system, intervene in the suppression of posture during REM sleep, as well as during the cataplectic episodes which occur in narcolepsy. These structures are under the modulatory (inhibitory) influence of the dorsomedial and the dorsolateral pontine tegmentum, where serotoninergic raphe nuclei (RN) neurons and noradrenergic locus coeruleus (LC) neurons are located. We postulated that M may act not only on the circadian pacemaker, but also directly on the pontine tegmental structures involved in the regulation of posture during the animal states indicated above. This hypothesis is supported by the facts that:
1) the dorsal pRF may contain specific binding sites for M;
2) this structure is particularly sensitive to M in adolescents, as well as in adult subjects affected by narcoleptic disturbances leading to cataplexy;
3) M increases the release of serotonin (5-HT), a neurotransmitter which enhances the postural tone by acting on the dorsal pRF: on the other hand, deficits in M levels may lower the activity of the serotoninergic raphe system, thus leading to a decrease or suppression of postural activity similar to that occurring either during REM sleep or during the cataplectic episodes typical of narcoleptic patients;
4) IS patients may show episodes of sleep apnea, a phenomenon which has been attibuted to a reduced tonic contraction of primary and accessory respiratory muscles during REM, resulting from a reduced release of 5-HT at dorsal pontine level. It has been postulated that, if the reduced M and 5-HT levels are subliminal to produce a complete suppression of posture under the conditions reported above, the reduced postural tone, which results from this condition may lead to the development of IS, due to hypotonia which affects the axial musculature. M secretion could be regulated not only by the activity of the serotoninergic raphe neurons projecting to the pineal gland, but probably also by the activity of noradrenergic LC neurons. It is likely that the development of IS, which results from a reduced level of M and 5-HT, may occur provided that the noradrenergic LC inhibition of the pontine structures is impaired. Such impairment could depend upon genetic factors, similar to those postulated to play a role in narcolepsy. In conclusion, the possibility exists that an impaired activity of brain monoaminergic systems may lead to disfunction in the production of M, which is apparently an important factor in the etiopathogenesis of IS.

Publication Types:

Review

Review, Academic

PMID: 12004644 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12019362&dopt=Abstract

Neuroendocrinol Lett 2002 Apr;23 Suppl 1:104-9

The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat.

Ostrowska Z, Kos-Kudla B, Marek B, Kajdaniuk D, Staszewicz P, Szapska B, Strzelczyk J.

Department of Clinical Biochemistry, Silesian Medical Academy, Zabrze, Poland. ozdrasiek@poczta.onet.pl

BACKGROUND AND OBJECTIVES: There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy.

METHODS: The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation).

RESULTS: The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown.

CONCLUSION: Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy.

PMID: 12019362 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12080285&dopt=Abstract
Neuroendocrinol Lett 2002 Jun;23(3):239-42

Circadian rhythm of melatonin in patients with colorectal carcinoma.

Kos-Kudla B, Ostrowska Z, Kozlowski A, Marek B, Ciesielska-Kopacz N, Kudla M, Kajdaniuk D, Strzelczyk J, Staszewicz P.


Department of Pathophysiology and Endocrinology, Silesian Medical University, Zabrze, Poland. PHONE/FAX: +48 32 2786126. beatakos@ka.onet.pl

OBJECTIVE: The aim of the study was pineal gland function assessment on the base of daily rhythm study and mean daily melatonin (MEL) concentrations in serum in patients with colorectal carcinoma.
MATERIAL AND METHODS: Studies were performed in 12 women at the age of 63.17+/-5.90 years and 21 men aged 58.95+/-11.32 years with large intestine adenocarcinoma. The control group consisted of 28 healthy volunteers at comparable age. During the circadian study blood samples for the measurement of melatonin (MEL) were collected every 4 hours during 12 h. MEL concentrations were assessed with the use of RIA methods. Statistical analysis of circadian rhythms of MEL was carried out with the use of cosinor method according to Halberg.
RESULTS: Existence of daily rhythm of MEL secretion was shown in all studied groups. A significant decrease of amplitude of rhythm and secretion of MEL at nocturnal hours in comparison with the control group was shown in the group of women with large intestine carcinoma. A significant decrease of mesor value and amplitude of MEL rhythm as a consequence of decrease of MEL secretion at nocturnal and morning hours was observed in the group of ill men.
CONCLUSIONS: Decrease in melatonin circadian rhythm amplitude as a consequence of its lowered nocturnal secretion occurred in all patients with colorectal carcinoma. Abnormalities in daily rhythm of melatonin secretion were more intensified in men with large intestine carcinoma, which leads to suppression of mean daily hormone concentration.

PMID: 12080285 [PubMed - in process]


Full report available free (in Spanish) at
http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0103&rev=37&vol=57&num=2&pag=121

An Esp Pediatr 2002 Aug;57(2):121-6

[Puberty and melatonin]

[Article in Spanish]

Murcia Garcia J, Munoz Hoyos A, Molina Carballo A, Fernandez Garcia JM, Narbona Lopez E, Uberos Fernandez J.

Departamento de Pediatria. Hospital Clinico Universitario San Cecilio. Granada. Espana.

Background. Melatonin is the main hormone secreted by the pineal gland and secretion is maximal at night. Although researchers disagree, numerous data suggest that elevated melatonin levels during the prepubertal age maintain the hypothalamic-pituitary-gonadal axis in quiescence, thus exerting an inhibitory effect on pubertal development. The decrease in serum melatonin with advancing age activates hypothalamic pulsatile secretion of gonadotropin-releasing hormone and consequently the reproductive axis, which results in the onset of puberty.
Objective To evaluate urinary melatonin levels in children of different ages and the characteristics of its rhythmic excretion and to determine whether puberty is associated with a significant reduction in urinary melatonin levels.
Material and methods Thirty-two children were studied (17 boys and 15 girls). Concentrations of 24-h urinary melatonin were quantified by radioimmunoassay in daytime samples (collected between 9.00 and 21.00) and nighttime samples (collected between 21.00 and 9.00 on the following day). Blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) were calculated. Circadian rhythms and melatonin secretion in the various Tanner stages were assessed (ANOVA).
Results No significant differences were found between day- and nighttime secretion of melatonin among boys (daytime melatonin: 1.38 0.52 pg/ml; nighttime melatonin: 6.92 2.06 pg/ml) and girls (daytime melatonin: 1.15 0.43 pg/ml; nighttime melatonin: 11.41 4.32 pg/ml). Highly significant differences were found (p < 0.001) between the day and night rates of melatonin secretion in both genders. Highly significant differences (p < 0.001) were also found in day-, nighttime and total secretion among the different Tanner stages. Comparison among groups revealed a significant decrease in secretion rates in stages I and II in both boys and girls. Melatonin significantly decreased with age in both sexes (lineal relationship). This decrease was greater at night. No relationship was found between the secretion of melatonin and estradiol, testosterone, LH, FSH and DHEAS.
Conclusions Melatonin secretion follows a circadian pattern, with greater secretion at night. The change in this rhythm was significantly greater in girls, due to greater nighttime secretion. Secretion significantly decreases in Tanner stages I and II with subsequent decreases in the later stages.

PMID: 12139866 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12495223&dopt=Abstract

Histochem J 2002 Mar-Apr;34(3-4):167-71

Id-1 expression defines a subset of vimentin/S-100beta-positive, GFAP-negative astrocytes in the adult rat pineal gland.

Kofler B, Bulleyment A, Humphries A, Carter DA.

School of Biosciences, Cardiff University, Cardiff CF10 3US, UK.

Id proteins are dominant negative members of the helix-loop-helix (HLH) transcription factor family which are involved in the differentation of many cell types, including glia. We have recently identified the adult rat pineal gland as a major site of Id-1 and Id-3 expression. In the present study, double fluorescence immunocytochemical analysis was used to examine the co-localization of Id-1 and Id-3 with both neuronal (synaptophysin, betaIII-tubulin) and astrocytic markers (GFAP, vimentin, S-100beta) in the rat pineal. In addition to localizing Id-1 and Id-3 protein to the melatonin-producing pinealocytes, we have also made the novel observation that Id-1, but not Id-3, is highly expressed in a population of vimentin-positive/S-100beta-positive/GFAP-negative astrocytes. Surprisingly, Id-1 was primarily cytoplasmic in these cells, and expression extended throughout the cellular processes. The pineal has been recognized previously as a unique region of the central nervous system in which a vimentin-positive/GFAP-negative glial phenotype is maintained in adult mammals. The exclusion of Id-1 from GFAP-positive cells, and expression in a population of vimentin-positive pineal astrocytes is evidence of a role for Id-1 in the adult stabilization of one form of astrocyte. These results identify the rat pineal gland as a model system for the functional analysis of Id-1.

PMID: 12495223 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11753388&dopt=Abstract

Nat Genet 2002 Jan;30(1):117-21

Otx5 regulates genes that show circadian expression in the zebrafish pineal complex.

Gamse JT, Shen YC, Thisse C, Thisse B, Raymond PA, Halpern ME, Liang JO.

Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland, 21210 USA.

The photoneuroendocrine system translates environmental light conditions into the circadian production of endocrine and neuroendocrine signals. Central to this process is the pineal organ, which has a conserved role in the cyclical synthesis and release of melatonin to influence sleep patterns and seasonal reproduction. In lower vertebrates, the pineal organ contains photoreceptors whose activity entrains an endogenous circadian clock and regulates transcription in pinealocytes. In mammals, pineal function is influenced by retinal photoreceptors that project to the suprachiasmatic nucleus-the site of the endogenous circadian clock. A multisynaptic pathway then relays information about circadian rhythmicity and photoperiod to the pineal organ. The gene cone rod homeobox (crx), a member of the orthodenticle homeobox (otx) family, is thought to regulate pineal circadian activity. In the mouse, targeted inactivation of Crx causes a reduction in pineal gene expression and attenuated entrainment to light/dark cycles. Here we show that crx and otx5 orthologs are expressed in both the pineal organ and the asymmetrically positioned parapineal of larval zebrafish. Circadian gene expression is unaffected by a reduction in Crx expression but is inhibited specifically by depletion of Otx5. Our results indicate that Otx5 rather than Crx regulates genes that show circadian expression in the zebrafish pineal complex.

PMID: 11753388 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12134360&dopt=Abstract

Rev Neurol 2002 May 1-15;34(9):898-9

No Abstract available

[Epidemiological study of pinealoma in Aragon and La Rioja]

[Article in Spanish]

Pascual-Piazuelo MC, Serrano-Ponz M, Bestue M.

PMID: 12134360 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12500161&dopt=Abstract

Neuroendocrinol Lett 2002 Oct-Dec;23(5-6):405-10

Effects of estradiol benzoate on the ultrastructure of the pinealocyte in the ovariectomized rat.

Kus I, Oner H, Ozogul C, Ayar A, Ozen OA, Sarsilmaz M, Kelestimur H.

Department of Anatomy, Faculty of Medicine, Firat University, Elazig, Turkey.

OBJECTIVE: The aim of this study was to examine the effects of ovariectomy and ovariectomy followed by estradiol benzoate administration on the ultrastructure of pinealocytes in female rat.
DESIGN: For this purpose 15 female Wistar rats were used. Animals were divided into three groups. Group I and II were designated as sham-ovariectomized (control) and ovariectomized, respectively. Group III was ovariectomized and daily injected with estradiol benzoate for one month. At the end of the experiment, all animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II and III were removed. All specimens were examined by electron microscopy.
RESULTS: Ovariectomy caused an increase of lipid droplets, mitochondria and ribosomes. Rough endoplasmic reticulum was extensive in the cytoplasm. Estradiol administration to ovariectomized rats resulted in formation of less extensive lipid droplets, mitochondria and ribosomes compared to pinealocyte ultrastructure of both control and ovariectomized rats. Extensiveness of rough endoplasmic reticulum in the pinealocytes of estradiol-administrated rats was similar to that in controls.
CONCLUSIONS: The results confirm relationship between the pineal gland and gonads in the rat and it has been suggested that estradiol benzoate reverses the ultrastructural changes, which indicate increased cell activation, occurring in the pinealocytes after ovariectomy.

PMID: 12500161 [PubMed - in process]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11993856&dopt=Abstract

Acta Histochem 2002;104(1):93-7

Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study.

Kus I, Akpolat N, Ozen OA, Songur A, Kavakli A, Sarsilmaz M.

Department of Anatomy, School of Medicine, Firat University, Elazyg, Turkey. ilterkus@hotmail.com

We have investigated immunohistochemically the effects of melatonin on Leydig cells in rat. Three groups of Wistar rats were used. Rats in group I and II were sham-pinealectomized (control) and pinealectomized, respectively, whereas rats in group III were pinealectomized and injected daily with melatonin for 2 months. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum testosterone levels were determined with the use of a chemiluminescent enzyme immunoassay. Testicular tissue was collected and processed for semiquantitative evaluation of immunohistochemical testosterone staining. Intensity of immunostaining was determined on a scale between 0 (no staining) and 5 (heavy staining). In pinealectomized rats, serum testosterone levels were significantly increased as compared to sham-pinealectomized rats. Daily administration of melatonin after pinealectomy resulted in significant decreased serum testosterone levels as compared to levels in control and pinealectomized rats. Immunostaining of testosterone was moderate (3+) in sham-pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in pinealectomized rats that were treated with melatonin, respectively. The results of our study indicate that pinealectomy induces increased testosterone secretion in Leydig cells and this increased secretion can be prevented by administration of melatonin.

PMID: 11993856 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11841595&dopt=Abstract

J Pineal Res 2002 Jan;32(1):15-20

Testicular activity is restored by melatonin replacement after suprachiasmatic nucleus lesion or superior cervical ganglionectomy in mink.

Maurel DL, Ben Saad MM, Roch G, Siaud P.

Pathologie de l'Oreille interne et Rehabilitation, INSERM, Faculte de Medecine Nord, Boulevard Pierre-Dramard, Marseille cedex 20, France. maurel.d@jean-roche.univ-mrs.fr

Subcutaneous melatonin implants were inserted in mink subjected to natural (autumn) or experimental gonadostimulatory short-days (4L:20D), after lesion of the suprachiasmatic nucleus (SCNx) or after superior cervical ganglionectomy (SCGx). Gonad stimulation was assessed by measuring testicular volume and plasma testosterone level. In SCNx and SCGx animals, all measurements were indicative of sexual quiescence. In contrast, both SCNx and SCGx animals with melatonin, maintained in natural or experimental gonadostimulating short-days, showed an increase in testicular activity 2 months after melatonin implantation. Thus, melatonin (and pineal activity) is a prerequisite for the photoperiodic stimulation of reproductive activity, and the SCN is not necessarily the target site for melatonin action on the renewal of reproduction in the mink.

PMID: 11841595 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12019362&dopt=Abstract

Neuroendocrinol Lett 2002 Apr;23 Suppl 1:104-9

The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat.

Ostrowska Z, Kos-Kudla B, Marek B, Kajdaniuk D, Staszewicz P, Szapska B, Strzelczyk J.

Department of Clinical Biochemistry, Silesian Medical Academy, Zabrze, Poland. ozdrasiek@poczta.onet.pl

BACKGROUND AND OBJECTIVES: There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy.
METHODS: The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation).
RESULTS: The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown.
CONCLUSION: Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy.

PMID: 12019362 [PubMed - indexed for MEDLINE]