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Pineal Gland Abstracts: 1997
Note: the following is a limited selection of abstracts available at PubMed, Science Direct, and Toxnet.
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J Am Acad Child Adolesc Psychiatry. 1997 Mar;36(3):412-6.Case study: melatonin in severe obesity.
Shafii M, MacMillan DR, Key MP, Kaufman N, Nahinsky ID.
Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, KY, USA.
Nocturnal serum melatonin was measured at half-hour intervals from 6:30 P.M. to 7 A.M. in two sisters, one severely obese 15-year-old and one somewhat overweight 12-year-old. Both, otherwise, were physically and psychiatrically healthy. In the severely obese sister, there was a significant increase in the serum melatonin mean level, a delayed phase-shift, and a delayed peak. Also, her overnight urine melatonin and its metabolite, 6-hydroxymelatonin sulfate, were significantly higher. Could there be a relationship between dysregulation of the pineal gland and severe obesity?
PMID: 9055523 [PubMed - indexed for MEDLINE]
Autoimmunity. 1997;26(1):43-53.
Melatonin, immune modulation and aging.
Zhang Z, Inserra PF, Liang B, Ardestani SK, Elliott KK, Molitor M, Watson RR.
Arizona Prevention Center, University of Arizona School of Medicine, Tucson 85724, USA.
Melatonin is a hormone secreted by the pineal gland in response to photoperiods and influences many important biological processes. For one, Melatonin has been shown to produce resistance to cancer and infectious diseases in aged animals. Studies in animals have demonstrated melatonin-related mechanisms of action on immunoregulation. Additionally, melatonin has been successfully used in humans, along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro studies show melatonin enhances both natural and acquired immunity in animals. Despite all of this intriguing evidence, melatonin's mechanism of action on the immune system is only partially defined. It does, however, appear to act through lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate immune cells. In order to understand immunomodulation and anti-cancer effects, information on melatonin and it's interactions with other endocrine hormones are summarized.Publication Types: Review; Review, Tutorial
PMID: 9556354 [PubMed - indexed for MEDLINE]
Wien Klin Wochenschr. 1997 Oct 3;109(18):730-6.
[Interaction of the epiphysis and the immune system]
[Article in German]
Liebmann PM, Wolfler A, Schauenstein K.
Institut fur Allgemeine und Experimentelle Pathologie, Universitat Graz, Osterreich.
First indications that the pineal gland may be involved in endocrine immunomodulation came from early reports on anti-tumor effects of pineal extracts in animals and humans. In the meantime, evidence has accumulated suggesting that melatonin, the major endocrine product of the pineal gland-as a well preserved molecule during evolution-is indeed involved in the feedback between neuroendocrine and immune functions. At present we are beginning to understand the mechanisms of action by which melatonin affects cellular functions, and from the variety of possible direct and indirect interactions it appears that melatonin may play a complex physiological role in neuroimmunomodulation. In this article we present a critical review of the numerous reports on the influence of melatonin on immune functions and discuss the possible underlying molecular pathways. In addition, a short comment is given on the current public discussion as to the clinical value of melatonin.
Publication Types: Review Review, Tutorial
PMID: 9441516 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9066504&dopt=Abstract
Int Arch Allergy Immunol. 1997 Mar;112(3):203-11.
Melatonin and the immune system.
Liebmann PM, Wolfler A, Felsner P, Hofer D, Schauenstein K.
Institute of General and Experimental Pathology, University of Graz, Austria.
In recent years, melatonin, i.e. the major endocrine product of the pineal gland, was investigated as to its possible regulatory role in the communication between the neuroendocrine and the immune systems. First indications that melatonin may be an endocrine immunomodulator came from early reports about antitumor effects in animals and humans. Since then evidence has accumulated suggesting that melatonin-as a well-preserved molecule during evolution-is indeed involved in the feedback between neuroendocrine and immune functions. At present we begin to discover molecular mechanisms, by which melatonin affects cellular functions in general, and from the variety of possible direct and indirect interactions it appears that melatonin may play a complex physiological role in neuroimmunomodulation. In this article we want to give a critical review of the numerous reports on melatonin influencing immune functions, and to discuss the possible different mechanisms of action, which were suggested recently.
Publication Types: * Review * Review, Academic
PMID: 9066504 [PubMed - indexed for MEDLINE]
Mol Cell Endocrinol. 1997 Dec 31;136(1):7-13.
Detection of melatonin and serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase activities in rat ovary.
Itoh MT, Ishizuka B, Kudo Y, Fusama S, Amemiya A, Sumi Y.
Department of Chemistry, St. Marianna University School of Medicine, Kawasaki, Japan.
Melatonin (N-acetyl-5-methoxytryptamine) and the activities of two melatonin-synthesizing enzymes, serotonin N-acetyltransferase (acetyl coenzyme A: arylalkylamine N-acetyltransferase EC 2.3.1.87; NAT) and hydroxyindole-O-methyltransferase (S-adenosyl-L-methionine: N-acetylserotonin-O-methyltransferase EC 2.1.1.4; HIOMT), were assayed in extracts of ovaries obtained from virgin Wistar-derived rats (7-9 week-old) during the light period of a 12 h light/12 h dark cycle. Melatonin was detected in the rat ovary using reverse-phase high-performance liquid chromatography (HPLC) coupled with fluorometric detection and radioimmunoassay (RIA). In addition, NAT and HIOMT activities were found in rat ovary. The apparent Michaelis constants (Km) for the substrates of NAT and HIOMT in the rat ovary were similar to those reported for the pineal gland and retina. These data suggest that the rat ovary, like the pineal gland and the retina, may synthesize melatonin from serotonin by the sequential action of NAT and HIOMT.
PMID: 9510062 [PubMed - indexed for MEDLINE]
Spine. 1997 Nov 15;22(22):2626-35.
Characterization of the scoliosis that develops after pinealectomy in the chicken and comparison with adolescent idiopathic scoliosis in humans.
Wang X, Jiang H, Raso J, Moreau M, Mahood J, Zhao J, Bagnall K.
Department of Surgery, University of Alberta, Edmonton, Canada.
STUDY DESIGN: The characteristics of the scoliosis that develops after pinealectomy in young chickens were determined from weekly posteroanterior radiographs. These data were compared with similar data collected from human patients with adolescent idiopathic scoliosis.
OBJECTIVES: To characterize the scoliosis produced in young chickens after pinealectomy and to compare these characteristics with those seen in human patients with adolescent idiopathic scoliosis.
SUMMARY OF BACKGROUND DATA: Although it has been recognized that pinealectomy produces scoliosis in chickens, the characteristics of these curves have never been well described other than by simple visual descriptions.
METHODS: The characteristics of the scoliosis produced in chickens after pinealectomy done 3 days after hatching were measured from radiographs taken at weekly intervals. These characteristics were compared with similar data collected from human patients with adolescent idiopathic scoliosis.
RESULTS: Similarities included development of single and double curves, degree of curvature, stability of the curve, numbers of vertebrae involved, direction of rotation, and progression characteristics. Differences included wedged vertebrae in the chickens, in conjunction with curve development and increased variability in vertebrae involved.
CONCLUSIONS: There are many similarities in the development of scoliosis in young chickens after pinealectomy and in children with adolescent idiopathic scoliosis. The few differences might be related to the different biomechanical properties associated with the spine in the two species.
PMID: 9399448 [PubMed - indexed for MEDLINE]
Clin Pediatr (Phila). 1997 Sep;36(9):543-5.
Pineal cyst in a girl with central precocious puberty.
Franzese A, Buongiovanni C, Belfiore G, Moggio G, Valerio G, Ciccarelli NP, Di Maio S.
Department of Pediatrics, University Federico II, Naples, Italy.
PMID: 9307090 [PubMed - indexed for MEDLINE]
Cell Mol Biol (Noisy-le-grand). 1997 May;43(3):409-16.
Ovarian granulosa and theca interstitial cells: a morphological and physiological analysis in guanethidine denervated rats at pre-puberty.
Rosa e Silva AA, Prajiante TM, Almeida FH, Guimaraes MA, Lunardi LO.
Department of Physiology, Faculty of Medicine of Ribeirao Preto, USP, Brazil.
Since ovary denervation causes delayed puberty, we investigated the relative importance of ovary innervation on the morphology and physiology of theca interstitial cells (TIC) and granulosa cells (GC) in female rats at pre-puberty. Elimination of the sympathetic innervation was performed by long term post natal treatment with guanethidine (GD), an adrenergic blocking agent. The sympathectomized rats exhibited: reductions in follicular volume (40%), granulosa cells area (43%) and theca interstitial cell volume (50%). Ovarian concentrations of pregnenolone (P5) and progesterone (P4) were decreased whereas no differences were observed in androstenedione (A) and estradiol (E2). The intensity of the immunocytochemical reaction for 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) detected only in interstitial cells, did not show any difference. These in vivo results include the TIC in the bulk of ovarian structures affected by GD denervation at pre-puberty as it was already observed for GC. The reduced area/volume occupied by these cells in the GD treated ovary is associated to a blockade of the initial steps of the steroidogenic pathway, probably at the level of the cholesterol side chain cleavage enzyme (P450 s.c.c.), previously to P5 synthesis, since P5 is reduced. Similar intra ovarian concentrations of androgens are discussed in terms of possible pineal deafferentation promoted by GD at high doses.
PMID: 9193796 [PubMed - indexed for MEDLINE]
Cell Mol Biol (Noisy-le-grand). 1997 May;43(3):383-91.
Male gonadal denervation by guanethidine at pre-puberty: different doses, different results. The intervention of the pineal deafferentation.
Guimaraes MA, Lunardi LO, Pellizzon CH, Kempinas WG, Rosa e Silva AA.
Department of Physiology, Faculty of Medicine-USP, Ribeirao Preto, Brazil.
Since gonadal denervation and pineal deafferentation by cervical superior ganglionectomy affect sexual development, this study was performed to evaluate testicular steroidogenesis, spermatogenesis and the cervical superior ganglion (CSG) histology in rats treated with guanethidine (GD). The treatment was performed by GD s.c. injections for 3 weeks, from the 21st day of age to the 41st day of age (pre-puberty), when the animals were sacrificed. Different doses were used: group A = 10 mg/kg/day, group B = 50 mg/kg/day and saline (control group). Testicular denervation was confirmed by HPLC for catecholamines in testicular tissue. Testicular concentrations (TC) of progesterone (P4) and testosterone (T) were measured by RIA. Significantly higher TC of P4 and lower TC of T were observed only in group A in comparison with group B and the control group. No alteration of sperm production was observed in either treated group. Histological analysis of CSG showed only few neuronal alterations in group A rats, while in group B the nervous cells were practically destroyed. This suggests that 10 mg/kg/day GD treatment probably produces a specific blockade of 17 alpha-hydroxylase/17,20 desmolase at pre-puberty leading to a decrease of the androgen production. However, in the 50 mg/kg/day group no differences were observed concerning the steroid profiles, this result being attributed to the extensive damage to the CSG observed only in group B. The CSG destruction causes deafferentation of the pineal gland producing abolishment of the inhibition of the 17 alpha-hydroxylase/17,20 desmolase promoted by melatonin or by an out of phase production of androgen.
PMID: 9193793 [PubMed - indexed for MEDLINE]
Full free article available at http://jcem.endojournals.org/cgi/content/full/82/3/977
J Clin Endocrinol Metab. 1997 Mar;82(3):977-81.
Luboshitzky R, Dharan M, Goldman D, Hiss Y, Herer P, Lavie P.
Department of Endocrinology, Central Emek Hospital, Afula, Israel.
Recently, we demonstrated that melatonin secretion was increased in male patients with GnRH deficiency and decreased to normal levels during testosterone treatment. These data suggested that gonadal steroids modulate melatonin secretion, probably by activating specific receptors in the pineal gland. We used immunohistochemistry to localize gonadotropin (LH and FSH) and gonadal steroid (androgens and estrogens) receptors in human pineal glands. Tissues were obtained at autopsy from 25 males, aged 19-87 yr, and five prepubertal children, aged 0.2-10 yr. Positive staining for all four types of receptors (LH, FSH, androgen, and estrogen) in the pineal parenchymal cells, pinealocytes, was evident in all 30 glands examined. Double staining revealed that nuclear receptors (androgen or estrogen) co-existed with cytoplasmatic receptors (LH or FSH) in the same cells. The results demonstrate the presence of gonadotropin and gonadal steroid receptors in human pinealocytes from infancy to old age.
PMID: 9062516 [PubMed - indexed for MEDLINE]
J Neuropathol Exp Neurol. 1997 Dec;56(12):1356-62.
The amyloid beta protein induces oxidative damage of mitochondrial DNA.
Bozner P, Grishko V, LeDoux SP, Wilson GL, Chyan YC, Pappolla MA.
Department of Pathology, University of South Alabama, Mobile 36617, USA.
Multiple lines of evidence suggest involvement of oxidative stress in the pathogenesis of Alzheimer disease (AD). The finding that amyloid beta peptide (A beta) has neurotoxic properties and that such effects are mediated in part by free-radicals has provided an avenue to explore new therapeutic strategies. In this study, we showed that exposure of PC 12 cells to an A beta fragment induces oxidative damage of mitochondrial DNA. Cells were exposed for 24 h to 50 microM A beta (25-35) or to 50 microM of a control peptide with a scrambled sequence. Oxidative damage of mitochondrial DNA (mtDNA) was assessed using a Southern blot technique and an mtDNA-specific probe recognizing a 13.5-kilobase restriction fragment. Treatment of DNA with NaOH was used to reveal abasic sites and single strand breaks. Treatment with endonuclease III or FAPy glycosylase was used to detect pyrimidine or purine lesions, respectively. Cells exposed to A beta exhibited marked oxidative damage of mtDNA as evidenced by characteristic changes on Southern blots. Cells exposed to the scrambled peptide did not show such modifications. Simultaneous addition of the pineal hormone melatonin consistently prevented the A beta-induced oxidative damage to mtDNA. Mitochondrial dysfunction in AD has been demonstrated by several laboratories. This study provides experimental evidence supporting a causative role of A beta in mitochondrial lesions of AD.
PMID: 9413284 [PubMed - indexed for MEDLINE]
Full free article available at http://www.jneurosci.org/cgi/content/full/17/5/1683
J Neurosci. 1997 Mar 1;17(5):1683-90.
Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide.
Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK.
Department of Pathology and Laboratory Medicine, University of South Alabama, Mobile, Alabama 36617, USA.
Studies from several laboratories have generated evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). The finding that the amyloid beta protein (Abeta) has neurotoxic properties and that such effects are, in part, mediated by free radicals has provided insights into mechanisms of cell death in AD and an avenue to explore new therapeutic approaches. In this study we demonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracellular Ca2+ increases induced by a cytotoxic fragment of Abeta. The effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including cell viability studies by confocal laser microscopy, electron microscopy, and measurements of intracellular calcium levels. The importance of this finding is that, in contrast to conventional antioxidants, melatonin has a proposed physiological role in the aging process. Secretion levels of this hormone are decreased in aging and more severely reduced in AD. The reported phenomenon may be of therapeutic relevance in AD.
PMID: 9030627 [PubMed - indexed for MEDLINE]
Brain Res. 1997 Mar 28;752(1-2):269-78.
High levels of human chymase expression in the pineal and pituitary glands.
Baltatu O, Nishimura H, Hoffmann S, Stoltenburg G, Haulica ID, Lippoldt A, Ganten D, Urata H.
Max-Delbruck-Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
The brain renin-angiotensin system plays a role in both cardiovascular homeostasis and neurosecretory functions. Since the mechanisms of angiotensin (Ang) II formation in the human brain have not been clarified, the aims of the present study were to determine the presence of human chymase and angiotensin I-converting enzyme (ACE) in human and non-human brains. In the human brain, the total Ang II-forming activity was significantly higher in the pineal and pituitary glands than those in other regions. In other species (rat, bovine and porcine), the level of chymase as well as total Ang II-forming activities in pineal glands were significantly lower than those in human glands. High levels of chymase-like immunoreactivity (ir) were found in the arteriolar endothelial cells, adventitial mesenchymal cells and in parenchymal cells of the human pineal and pituitary glands while ACE-ir was mostly observed in the endothelial cells and occasionally found in parenchymal cells. Our study provides the first evidence that human chymase exists in the pineal and pituitary glands. The remarkable regional and species differences in mechanisms of Ang II formation suggest a specific role of chymase or ACE in the human brain.
PMID: 9106467 [PubMed - indexed for MEDLINE]
Biochim Biophys Acta. 1997 Mar 15;1334(2-3):214-22.
Regional distribution and postnatal changes of D-amino acids in rat brain.
Hamase K, Homma H, Takigawa Y, Fukushima T, Santa T, Imai K.
Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Japan.
Regional distribution of D-amino acids in rat brain was studied by the modified highly sensitive analytical method which was previously developed. The method includes fluorogenic derivatization of each amino acid, isolation of each amino acid by reverse-phase HPLC, followed by enantiomeric separation with Pirkle-type chiral stationary phases. D-Amino acid contents were determined in the cerebrum, cerebellum, hippocampus, medulla oblongata, pituitary gland and pineal gland. D-Aspartic acid was observed in the pineal gland (3524 +/- 263 nmol/g, data are for male rats of 6 weeks of age) and the pituitary gland (80.5 +/- 9.0 nmol/g). D-Serine was found in various regions of the brain except for the cerebellum and medulla oblongata. D-Alanine was observed exclusively in the pituitary gland (25.9 +/- 4.4 nmol/g), whereas D-leucine was found in the pineal gland (3.4 +/- 0.4 nmol/g) and the hippocampus (1.6 +/- 0.07 nmol/g). No other D-amino acids were detected in the brain. The contents of D-aspartic acid in the pituitary gland and D-serine in the pineal gland were higher in female rats. In contrast the contents of D-alanine in the pituitary gland and D-leucine in the pineal gland and the hippocampus were higher in males. Postnatal changes of D-aspartic acid and D-leucine in the pineal gland and D-alanine in the pituitary gland were also investigated. The results described in this paper suggested that distinct regulatory mechanisms exist for individual D-amino acids in the corresponding region of rat brain.
PMID: 9101716 [PubMed - indexed for MEDLINE]
Biol Signals. 1997 Jul-Dec;6(4-6):181-312.
Recent Progress of Pineal Research--40 Years After Discovery of Melatonin. Proceedings of the AsiaPacific Pineal Meeting. Hamamatsu, Japan, March 28-31, 1997.
[No authors listed]
Publication Types: Congresses Overall
PMID: 9556366 [PubMed - indexed for MEDLINE]
Eur J Neurosci. 1997 Dec;9(12):2687-701.
The expression pattern of the orphan nuclear receptor RORbeta in the developing and adult rat nervous system suggests a role in the processing of sensory information and in circadian rhythm.
Schaeren-Wiemers N, Andre E, Kapfhammer JP, Becker-Andre M.
Institute for Brain Research, University of Zurich, Switzerland.
RORbeta is an orphan nuclear receptor related to retinoid and thyroid hormone receptors and is exclusively expressed in the central nervous system (CNS). Here we present an in situ hybridization analysis of the distribution of RORbeta mRNA in the developing and adult rat CNS. The receptor localizes to areas involved in the processing of sensory information. In the cerebral cortex, RORbeta mRNA was exclusively detected in non-pyramidal neurons of layer IV and, less so, layer V. The highest expression was found in primary sensory cortices. In the thalamus highest RORbeta expression was found in the sensory relay nuclei projecting to the respective cortical areas. In contrast, sensory projection neurons in the periphery, for example retinal ganglion cells and neurons of the sensory ganglia showed only little RORbeta expression. RORbeta is also expressed in areas involved in the generation and maintenance of circadian rhythms - the suprachiasmatic nucleus, the pineal gland and the retina. In the latter two tissues, RORbeta mRNA abundance oscillates with circadian rhythmicity peaking during the hours of darkness. RORbeta mRNA could not be detected in striatum, hippocampus, cerebellum, the motor nuclei of the cranial nerves or the ventral part of the spinal cord. During development, RORbeta is expressed in many areas as early as embryonic day (E) 15, anticipating the distribution pattern in the adult. Our data suggest that RORbeta regulates genes whose products play essential roles in the context of sensory input integration as well as in the context of circadian timing system.PMID: 9517474 [PubMed - indexed for MEDLINE]
Minerva Ginecol 1997 Jan-Feb;49(1-2):43-8
[The role of the pineal body in the endocrine control of puberty]
[Article in Italian]
Aleandri V, Spina V, Ciardo A.
I Istituto di Clinica Ostetrica e Ginecologica, Cattedra di Fisiopatologia della Riproduzione Umana, Universita degli Studi di Roma La Sapienza.
The pineal gland plays an important role in reproductive endocrinology. The epiphysis regulates seasonal variations in reproductive function of seasonally breeding animals. In humans, even if they are not seasonal breeders, the role of the pineal in reproductive endocrinology seems to be important as well. It appears to be of particular importance the endocrine control of the gland on pubertal sexual maturation. Even if not all researchers agree, several data suggest that elevated melatonin levels-characteristic of prepubertal age-keep the hypothalamic-pituitary-gonadal axis in quiescence: thus, an inhibitory effect on pubertal development is exerted. Subsequently, the decreasing serum melatonin with advancing age would result in activation of the hypothalamic pulsatile secretion of GnRH- and therefore of the reproductive axis-with consequent onset of pubertal phenomena. The production rate of melatonin does not change with age and no growth in pineal size from 1 to 15 years of age has been demonstrated by nuclear magnetic resonance (NMR) studies. Therefore the decrease of serum melatonin concentrations has been proposed to be due to the increase in body mass or, according to another hypothesis, to be also temporally linked to sexual maturation. Furthermore, recently, it has been suggested in rats that the pineal influences not only the pubertal sexual maturation, but even the gonadal and genital development and function of offspring, already during intrauterine life. Investigations are needed to evaluate this hypothesis in humans.
Publication Types:
Arzneimittelforschung. 1997 Nov;47(11):1271-3.
Survey of spontaneous dystrophic mineralisation of pineal gland in ageing rats.
Majeed SK.
Huntingdon Life Sciences, Department of Pathology, Cambridgeshire, UK.
The survey included 151 rats from several carcinogenicity studies up to 104 weeks and 260 rats from short-term studies up to 52 weeks. All studies were performed during the period 1990-1996. Young rats up to 52 weeks of age showed normal structural appearance, in 134 male rats the incidence of mineralisation was 6.3% and in 126 females the incidence was only slightly less at 5.6%. In ageing rats, 70-104 weeks, 88 males and 63 females showed far higher incidence of mineralisation, 83% and 57% respectively, showing that the incidence of mineralisation in ageing rats was higher in males than females. The focal mineralisation occurred mainly at the margin of the gland in the subcapsular region mostly adjacent to small blood vessels. On occasions these involved the parenchymal cells in the middle part of the gland. The focal mineralisation stained positive with von Kossa indicating presence of calcium and also with PAS (Pariodic Acid-Schiff method), indicating presence of neutral mucopolysaccharide. There was no evidence of positivity with Perl's stain (for ferric salts), Toluidine blue (for protein) or Alcian blue (for acid mucopolysaccharides). With Oil Red O there was evidence of presence of fat or lipid in pinealocytes.
PMID: 9428987 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9376799&dopt=Abstract
Dokl Akad Nauk. 1997 Aug;355(6):834-7.[Characteristics of structural and functional organization of the rat pineal gland depending on age]
[Article in Russian]
No Abstract available
Novikova IA, Kovalenko RI, Krasnoshchekova EI, Nozdrachev AD.
PMID: 9376799 [PubMed - indexed for MEDLINE]
Genetika 1997 Aug;33(8):1144-8
[Circadian rhythm of biosynthetic activity of the epiphysis in relatively wild and domesticated silver foxes]
[Article in Russian]
Kolesnikova LA.
Circadian dynamics of biosynthetic activity in pineal glands of adult relatively wild and domesticated silver fox females was studied beyond the reproductive season using radioimmune and fluorometric methods. The level of melatonin, the principal pineal hormone; activities of enzymes controlling its biosynthesis; the level of its precursor and one of its metabolites, as well as those of neurotransmitters involved in the regulation of biosynthesis exhibited more or less pronounced circadian changes. The concentration of melatonin in the pineal gland at night was considerably higher in domesticated foxes than in relatively wild ones. The most likely reason for the elevated concentration of melatonin at night is its slow secretion from the pineal glands of domesticated foxes, because its concentration in plasma does not differ from that in relatively wild animals. The results obtained suggest that selection for domestic behavior has affected the adrenergic mechanism of regulation of pineal gland rhythms, as well as other functions of sympathetic divisions of the central nervous system.
PMID: 9378307 [PubMed - indexed for MEDLINE]
No Abstract Available
N Engl J Med 1997 Jan 16;336(3):186-95
Melatonin in humans.
Brzezinski A.
Department of Obstetrics and Gynecology, Hebrew University Hadassah Medical School, Jerusalem, Israel.
Publication Types:
Am J Physiol. 1997 Sep;273(3 Pt 2):H1530-6.
Melatonin directly constricts rat cerebral arteries through modulation of potassium channels.
Geary GG, Krause DN, Duckles SP.
Department of Pharmacology, College of Medicine, University of California, Irvine 92697-4625, USA.
The pineal hormone melatonin was found to decrease luminal diameter of rat middle cerebral artery segments, pressurized in vitro, in a concentration-dependent manner (concentration that produced a half-maximal effect = 2.7 nM). Contractile responses to melatonin were inhibited by luzindole, a melatonin receptor antagonist, but not by the serotonin receptor antagonist ketanserin. Pertussis toxin abolished the effect of melatonin, which is consistent with involvement of Gi or G(o) protein-coupled receptors. The maximal effect of melatonin was increased by elevating transmural pressure. When compared at the same pressure, contractions elicited by melatonin were smaller than those elicited by serotonin but similar in magnitude to those produced by tetraethylammonium or charybdotoxin, blockers of Ca(2+)-dependent, large-conductance K+ (BKCa) channels. The effect of melatonin was significantly attenuated in the presence of BKCa channel blockers, but not by apamin, a blocker of Ca(2+)-dependent, small-conductance K+ channels. Melatonin, like tetraethylammonium, significantly reduced vasodilation produced by NS-1619, an opener of BKCa channels. Contractile responses to melatonin were diminished in the presence of elevated extracellular K+ (16 mM), but they were not significantly affected by NG-nitro-L-arginine methyl ester. The results suggest that activation of melatonin receptors on rat cerebral arteries increases vascular tone through Gi or G(o) protein-mediated inhibition of BKCa channels. Thus melatonin, which is secreted during the night, can directly influence the contractile state of cerebral arteries.
PMID: 9321846 [PubMed - indexed for MEDLINE]
J Pineal Res 1997 Jan;22(1):33-41
Nocturnal changes in pineal melatonin synthesis during puberty: relation to estrogen and progesterone levels in female rats.
Okatani Y, Watanabe K, Morioka N, Hayashi K, Sagara Y.
Department of Obstetrics and Gynecology, Kochi Medical School, Japan.
Our objective was to evaluate the changes in melatonin synthesis during the peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthesis. Pineal levels of tryptophan, 5-hydroxytryptamine (5-HT), melatonin and norepinephrine were determined in female Sprague Dawley rats (between 2 and 12 weeks of age) in the mid-dark during the daily light/dark cycle. Melatonin levels increased with age, parallel to pineal growth, until 6 weeks of age, when the vaginal opening was found in 66.7% of rats, and significantly decreased until 8 weeks of age, when the vaginal opening was found in all rats. Norepinephrine began to increase earlier and reached a mature level at 4 weeks of age. Treatments with bilateral ovariectomy at 4, 6, and 8 weeks of age resulted in significant increases in melatonin and 5-HT levels, and significant decrease in tryptophan level at 2 weeks after ovariectomy. Treatments with ovariectomy at 6 weeks of age produced a consistent increase in 5-HT level and a consistent decrease in tryptophan level until 6 weeks after ovariectomy. However, melatonin levels increased until 2 weeks after ovariectomy, then decreased and reached a control level at 6 weeks after ovariectomy. Subcutaneous implantation of estradiol-17 beta capsule and daily subcutaneous injection of estradiol benzoate (E2B) (1.0 microgram, 20 micrograms) for two weeks in the rats ovariectomized at 4, 6, and 8 weeks of age resulted in significant decreases in melatonin and 5-HT levels and a significant increase in tryptophan level at 2 weeks after ovariectomy. A smaller dose of E2B (0.1 microgram) produced the same effects in the rats ovariectomized at 4, but not at 6 and 8 weeks of age. Administration of progesterone (200 micrograms/day) for 2 weeks did not produce any significant changes in melatonin, 5-HT, and tryptophan levels. Norepinephrine levels were not changed by any of the above treatments. These results suggest that estrogen, but not progesterone, can modulate nocturnal pineal melatonin synthesis in peripubertal female rats, and that the decline in the melatonin synthetic activity during the pubertal period might be related to the increasing levels of endogenous estrogen, which is secreted from the maturing ovary. The sites of action of the inhibitory effect of estrogen on the pineal melatonin synthesis may be multiple.
PMID: 9062868 [PubMed - indexed for MEDLINE]
Horm Res 1997;47(3):97-101
Melatonin and 6-hydroxymelatonin sulfate excretion is inversely correlated with gonadal development in children.
Commentz JC, Uhlig H, Henke A, Hellwege HH, Willig RP.
Universitatskinderklinik Hamburg-Eppendorf, Deutschland.
To delineate the development of melatonin (MLT) production during childhood, we measured the excretion of MLT and 6-hydroxymelatonin sulfate (MLTS) in the urine of children (n = 134) from the 26th week of gestation until the age of 20 years. MLTS excretion showed a diphasic pattern with declining values in preterm babies with lowest values around term. After birth, the values remained low for the first 6 months of life. The highest values were reached between 4 and 7 years of age with a smooth but steady decline thereafter. A night-day difference was not detectable before the age of 6 months; the greatest night-day variations occurred at the time of the highest MLTS excretions. The MLT values showed an identical pattern but with amounts 1,000 times smaller; the ratio of MLTS to MLT increased from 40:1 in preterm babies to 900:1 in prepubertal children. In summary, the MLT/MLTS excretion exhibits the highest activity with respect to total secretory capacities as well as night-day differences at the time of gonadal quiescence during childhood. The strong inverse correlation of MLT and MLTS excretion with the hypothalamic-pituitary-gonadal activity points to a causal relationship between pineal gland activity and pubertal development.
PMID: 9050947 [PubMed - indexed for MEDLINE]
J Neuroimmunol. 1997 Jun;76(1-2):117-31.
Enriched immune-environment of blood-brain barrier deficient areas of normal adult rats.
Pedersen EB, McNulty JA, Castro AJ, Fox LM, Zimmer J, Finsen B.
Department of Anatomy and Cell Biology, University of Odense, Denmark. erikbo@imbmed.ou.dk
The circumventricular organs (CVOs) in the brain are without a blood-brain barrier (BBB) and as such directly exposed to blood plasma constituents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we initiated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens within the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement receptor type 3 immunoreactive microglial/macrophage cells expressed major histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the MHC class II antigen expressing cells could be grouped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was preferentially expressed by macrophage-like cells. MHC class I antigen was expressed by the vascular endothelium in both BBB-protected and BBB-deficient areas and was additionally present as a lattice-like network throughout the BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood-borne macrophages, possess an intrinsic immune surveillance system based on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.
PMID: 9184641 [PubMed - indexed for MEDLINE]
Cell Tissue Res. 1997 Jun;288(3):435-9.
A possible role of collagen fibrils in the process of calcification observed in the capsule of the pineal gland in aging rats.
Humbert W, Cuisinier F, Voegel JC, Pevet P.
CNRS-URA 1332, Neurobiologie des Fonctions Rythmiques et Saisonnieres, Universite Louis Pasteur, 12 Rue de l'Universite, F-67000 Strasbourg, France. whumbert@neurochem.u-strasbg.fr
The relationship between collagen fibrils and calcified concretions exclusively appearing in the pineal gland of adult/aging rats has been investigated. Deposits of lanthanum, which replace calcium ions are distributed along collagen fibrils with a repeating period of about 70 nm. Calcium has been detected histochemically between collagen bundles surrounding extracellular concretions by means of the pyroantimonate method and by X-ray microanalysis. It is associated with phosphorus. The data presented here suggest that collagen fibrils are involved in the genesis and growth of extracellular concretions located in the connective tissue surrounding the pineal gland of aging rats.
PMID: 9134857 [PubMed - indexed for MEDLINE]
Braz J Med Biol Res. 1997 Mar;30(3):305-13.
Evolution of circadian organization in vertebrates.
Menaker M, Moreira LF, Tosini G. NSF
Center for Biological Timing, University of Virginia, Charlottesville 22903, USA. mm7e@virginia.edu
Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations:i) in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN),
ii) in many non-mammalian vertebrates of all classes (but not in any mammals) the pineal gland is both a photoreceptor and a circadian oscillator, andiii) in all non-mammalian vertebrates (but not in any mammals) there are extraretinal (and extrapineal) circadian photoreceptors.An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates.
Publication Types: * Review * Review, Tutorial
PMID: 9246228 [PubMed - indexed for MEDLINE]
Arch Ital Biol. 1997 Mar;135(2):183-94.
Cell physiology of the pineal body.
Marchiafava PL, Kusmic C, Longoni B, Strettoi E.
Dipartimento di Fisiologia e Biochimica, Universita di Pisa, Italy.
The results from recent experiments on the cellular physiology of the trout pineal photoreceptors are briefly reviewed. The arguments are mainly concerned with pineal phototransduction. These studies have stimulated further research on melatonin, a molecule produced in pineal as well as in retinal photoreceptors. A discussion follows on our actual research object, that is a study of the influences of endogenous melatonin upon retinal receptor cells activities.
Publication Types: * Review * Review, Tutorial
PMID: 9101028 [PubMed - indexed for MEDLINE]
Ann Univ Mariae Curie Sklodowska [Med] 1997;52:9-13
[The dimensions of tectal lamina and subpineal triangle for ages 18-91]
[Article in Polish]
Macech B.
Katedra i Zaklad Anatomii Prawidlowej Czlowieka Akademii Medycznej w Lublinie.
The studies were performed in 144 individuals, 72 male and 72 female. The median and horizontal dimensions of tectal lamina and subpineal triangle were measured. The variations observed depended on sex and age. The results were compiled in tables and presented graphically.
PMID: 10023150 [PubMed - indexed for MEDLINE]Neurobiology (Bp). 1997;5(4):459-67. Related Articles, Links
Mediator substances of the pineal neuronal network of mammals.
Debreceni K, Manzano e Silva MJ, Ghosh M, Haldar C, Vigh B.
Department of Human Morphology and Developmental Biology, Semmelweis University of Medicine, Budapest, Hungary.
In addition to receptor-type pinealocytes, the mammalian pineal organ contains small and large neurons and ependymal/glial cells as well. Axons of pinealocytes form synaptic ribbon-containing axo-dendritic synapses on large secondary pineal neurons and/or terminate as neurohormonal endings on the basal lamina of the vascular surface of the organ. The small pineal neurons were found to be gamma-aminobutyric acid (GABA)-immunoreactive, while large secondary neurons and pinealocytes contained immunoreactive amino acids (glutamate and aspartate). Glutamate accumulated presynaptically in pinealocytic axon terminals on large secondary neurons and in the axons of these neurons. Glutamate immunoreactive axons of pineal neurons were traced via the pineal tract to the habenular nucleus. Axons containing granular vesicles and coming from extrapineal perikarya are glutamate immunoreactive as well. Aspartate and GABA are also present in some of the myelinated axons, supposedly pinealopetal in the pineal tract.
Publication Types: Review; Review, Tutorial
PMID: 9591281 [PubMed - indexed for MEDLINE]
Biol Signals. 1997 Jul-Dec;6(4-6):241-6.
Melatonin excretion rhythms in the cultured pineal organ of the lamprey, Lampetra japonica.
Samejima M, Tamotsu S, Uchida K, Moriguchi Y, Morita Y.
Department of Physiology, Hamamatsu University School of Medicine, Japan.
Pineal organ of the lamprey, Lampetra japonica, is essential to keep the circadian locomotor activity rhythm as previously reported. In this paper, we tried to show that an endogenous oscillator is located and is working in the pineal organ. When the pineal organs were excised and cultured in a plastic tube with M199 medium at 20 degrees C, melatonin secretion rhythms were clearly observed under both light-dark and continuous dark conditions. The circadian secretion of melatonin continued for more than five cycles under the continuous dark condition. This indicates that the pineal organ has an endogenous oscillator and that the melatonin secretion rhythm is controlled by this oscillator. These findings suggest the possibility that the locomotor activity rhythm of the lamprey is under the control of the oscillator in the pineal organ.
PMID: 9500662 [PubMed - indexed for MEDLINE]
Life Sci. 1997;60(10):PL169-74.
Melatonin is a scavenger of peroxynitrite.
Gilad E, Cuzzocrea S, Zingarelli B, Salzman AL, Szabo C.
Children's Hospital Medical Center, Division of Critical Care, Cincinnati, Ohio 45229, USA.
Peroxynitrite is a toxic oxidant formed from the reaction of superoxide and nitric oxide under conditions of inflammation and oxidant stress. Here we demonstrate that the pineal neurohormone melatonin inhibits peroxynitrite-mediated oxidant processes. Melatonin caused a dose-dependent inhibition of the oxidation of dihydrorhodamine 123 to rhodamine in vitro. Moreover, in cultured J774 macrophages, melatonin inhibited the development of DNA single strand breakage in response to peroxynitrite and reduced the suppression of mitochondrial respiration. Thus, melatonin appears to be a scavenger of peroxynitrite. This action may contribute to the antioxidant and antiinflammatory effects of melatonin in various pathophysiological conditions.
PMID: 9064472 [PubMed - indexed for MEDLINE]
Am J Epidemiol. 1997 Dec 15;146(12):1037-45.
Magnetic fields of transmission lines and depression.
Verkasalo PK, Kaprio J, Varjonen J, Romanov K, Heikkila K, Koskenvuo M.
Department of Public Health, University of Helsinki, Finland.
Electromagnetic fields have been suggested to contribute to the risk of depression by causing pineal dysfunction. Some epidemiologic studies have supported this possibility but have generally reported crude methods of exposure assessment and nonsystematic evaluation of depression. Using two available nationwide data sets, the authors identified from the Finnish Twin Cohort Study 12,063 persons who had answered the 21-item Beck Depression Inventory of self-rated depressive symptoms in 1990. The personal 20-year histories of exposure (i.e., distance and calculated annual average magnetic fields) before 1990 to overhead 110- to 400-kv power lines were obtained from the Finnish Transmission Line Cohort Study. The adjusted mean Beck Depression Inventory scores did not differ by exposure, providing some assurance that proximity to high-voltage transmission lines is not associated with changes within the common range of depressive symptoms. However, the risk of severe depression was increased 4.7-fold (95% confidence interval 1.70-13.3) among subjects living within 100 m of a high-voltage power line. This finding was based on small numbers. The authors recommend that attempts be made to strive for a better understanding of the exposure characteristics in relation to the onset and course of depression.
PMID: 9420528 [PubMed - indexed for MEDLINE]
Cancer Res. 1997 May 15;57(10):1909-14.
Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway.
Blask DE, Wilson ST, Zalatan F.
Bassett Research Institute, Cooperstown, New York 13326-1394, USA.
Melatonin, the chief hormone secreted by the pineal gland, has been previously shown to inhibit human breast cancer cell growth at the physiological concentration of 1 nM in vitro. In this study, using the estrogen receptor (ER)-positive human breast tumor cell line MCF-7, we have shown that 10 microM L-buthionine-[S,R]-sulfoximine (L-BSO), an inhibitor of gamma-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis), blocks the oncostatic action of 1 nM melatonin over a 5-day incubation, indicating that glutathione is required for melatonin action. The result was repeated with ZR75-1 cells, suggesting that the glutathione requirement is a general phenomenon among ER+ breast cancer cells. Addition of exogenous glutathione (1 microM) to L-BSO-treated groups restored the melatonin response in both cell lines. Further demonstration of the importance of glutathione was shown using the ER- breast tumor cell line HS578T, which is normally unresponsive to melatonin. Growth in this cell line was inhibited in the presence of 1 microM ethacrynic acid (an inhibitor of glutathione S-transferase) plus 1 nM melatonin, and this effect was blocked with 10 microM L-BSO. We also observed a steady decrease of intracellular glutathione in MCF-7 cells over a 5-day incubation, suggesting that these cells metabolize glutathione differently than do normal cells.
PMID: 9157984 [PubMed - indexed for MEDLINE]
J Endocrinol. 1997 Nov;155(2):305-12.
Differential adrenergic regulation of rat pineal cyclic AMP production and N-acetyltransferase activity during postnatal development: involvement of G alpha s and G alpha i1-2 proteins.
Harmouch A, Guerrero JM, Pozo D, Rafii-el-Idrissi M, Calvo JR, Reiter RJ, Osuna C.
Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Spain.
We have studied why rat pineal N-acetyltransferase (NAT) activity is relatively insensitive to isoproterenol in young rats when compared with adult rats. We report that activation by isoproterenol of pineal cyclic AMP production and NAT activity is higher in adult than in 2-week-old rats. However, the effect of dibutyryl cyclic AMP, which enters the pinealocyte and duplicates the effect of cyclic AMP, on NAT activity was similar at both ages. Moreover, we found that both alpha- and beta-adrenergic receptors are highly specific at both ages, since the binding of the specific radioligands used to their receptors could be displaced only by their corresponding agonists and antagonists. However, we observed differences between pineals from young and adult rats when several families of the alpha subunit of G-proteins were studied in cell membranes. ADP-ribosylation and immunoblot studies have shown clear differences in both 42 and 45 kDa forms of the Gs alpha Both forms exhibit low values in pineals from 2-week-old animals when compared with 6-week-old. We also show that the later appearance of both Gs alpha forms is roughly similar to the potent activation of cyclic AMP production and NAT activity in adult rats when compared with young rats. In conclusion, the results presented suggest that the relative lack of sensitivity of rat pineal gland to beta-adrenergic receptor agonists early in the postnatal development may be explained by the low levels of membrane Gs alpha, rather than postreceptor-mediated mechanisms or changes in the characteristics of the beta-adrenergic receptors on the pinealocyte membrane.
PMID: 9415065 [PubMed - indexed for MEDLINE]
Biol Signals. 1997 Jul-Dec;6(4-6):272-83.
Melatonin receptors in the spinal cord.
Pang SF, Wan Q, Brown GM.
Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.
The pineal hormone, melatonin, plays an important role in the regulation of diurnal and seasonal rhythms in animals. In addition to the well established actions on the brain, the possibility of a direct melatonin action on the spinal cord has to be considered. In our laboratory, we have obtained data suggesting that melatonin receptors are present in the spinal cords of birds and mammals. Using radioreceptor binding and quantitative autoradiography assays with 2-[125I]iodomelatonin as the specific melatonin agonist, melatonin binding sites have been demonstrated in the rabbit and chicken spinal cords. These sites are saturable, reversible, specific, guanosine nucleotide-sensitive, of picomolar affinity and femtomolar density. The linearity of Scatchard plots of saturation data and the unity of Hill coefficients indicate that a single class of melatonin binding sites is present in the spinal cord membranes studied. The picomolar affinity of these sites is in line with the circulating levels of melatonin in these animals suggesting that these sites are physiologically relevant. Autoradiography studies in the rabbit spinal cord show that melatonin binding sites are localized in the central gray substance (lamina X). In the chicken spinal cord, these binding sites are localized in dorsal gray horns (laminae I-V) and lamina X. As lamina X and laminae I-II have similar functions, melatonin may have comparable roles in the chicken and rabbit spinal cords. Moreover, in the chicken spinal cord, the density of 2-[125I]iodomelatonin binding in the lumbar segment was significantly higher than those of the cervical and thoracic segments. The densities of these binding sites changed with environmental manipulations. When chickens were adapted to a 12L/12D photoperiod and sacrificed at mid-light and mid-dark, there was a significant diurnal variation in the density (maximum number of binding sites; Bmax) of melatonin binding sites in the spinal cord. After constant light treatment or pinealectomy, the Bmax of melatonin receptors in the chicken spinal cord increased significantly in the subjective mid-dark period. Moreover, there was an age-related decrease in the 2-[125I]iodomelatonin binding to the chicken spinal cord. Our results suggest that melatonin receptors in the chicken spinal cord are regulated by environmental lighting and change with development. These receptors may play an important role in the chronobiology of spinal cord function. The biological responses of melatonin on spinal cords have also been demonstrated in vitro. Melatonin decreased the forskolin-stimulated cAMP production in the chicken spinal cord explant. Preincubation with pertussis toxin blocked the melatonin effect. Our results suggest that melatonin receptors in the chicken spinal cord are linked to the adenylate cyclase via a pertussis toxin-sensitive G protein and that melatonin binding sites in spinal cords are melatonin receptors with biological functions. These receptors may be involved in the regulation of spinal cord functions related to sensory transmission, visceral reflexes and autonomic activities.
Publication Types: Review; Review, Tutorial
PMID: 9500666 [PubMed - indexed for MEDLINE]