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Pineal Gland Abstracts: 2000
Note: the following is a limited selection of abstracts available at PubMed, Science Direct, and Toxnet.
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Arch Androl 2000 Sep-Oct;45(2):119-24
Ultrastructural interrelationship between the pineal gland and the testis in the male rat.
Kus I, Sarsilmaz M, Ogeturk M, Yilmaz B, Kelestimur H, Oner H.
Department of Anatomy, Firat University Medical School, Elazig, Turkey.
The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.
PMID: 11028930 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11455362&dopt=AbstractNeuroendocrinol Lett 2000;21(4):301-306
Melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary-gonadal axis in the rat.
Yilmaz B, Kutlu S, Mogulkoc R, Canpolat S, Sandal S, Tarakci B, Kelestimur H.
Firat University, Medical School, Department of Physiology, Department of Histology, 23119 Elazig, Turkey. b.yilmaz@excite.com
OBJECTIVES: We have investigated the changes in serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone levels together with testicular histology in both pinealectomized (PNX) and intact rats.
MATERIAL and METHODS: Twenty-one animals were PNX and allowed to recover for two months. Group I was assigned as PNX, group II PNX+melatonin and group III PNX+Human Chorionic Gonadotropin (HCG). Rats in group IV were sham PNX (S-PNX). An intact group of animals was s.c. injected with melatonin (0.5 mg/kg/day), another group with a combination of melatonin+HCG (5000 IU/kg/day) for seven days. Controls received saline alone (1 ml/kg). At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were determined by Radioimmunoassay, testosterone values by Chemiluminescent Enzyme Immunassay. Testicular tissue was collected and processed for light microscopy.
RESULTS: Serum LH levels were increased following PNX, but no such increases were seen in testosterone. In the PNX+melatonin group, serum LH and testosterone values were found to be similar to those of S-PNX group. HCG supplementation to PNX rats resulted in significant decreases in LH (p<0.005), but increased testosterone levels (p<0.001). Melatonin administration to intact animals significantly decreased both LH and testosterone levels (p<0.01). Co-administration of HCG+melatonin resulted in significant decreases in LH (p<0.001) and increases in testosterone levels (p<0.01). Serum FSH values did not show significant changes among groups. Only HCG administration significantly reduced FSH levels (p<0.01).
CONCLUSIONS: Our results suggest that melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary axis. There is a functional relationship and feedback regulation between the pineal gland and the testes.
PMID: 11455362 [PubMed - as supplied by publisher]
Full free report available at http://www.pnas.org/cgi/content/full/97/10/5586Proc Natl Acad Sci U S A 2000 May 9;97(10):5586-91
Establishment and persistence of photoperiodic memory in hamsters.
Prendergast BJ, Gorman MR, Zucker I.
Department of Psychology, University of California, Berkeley, CA 94720, USA. brianp@jhu.edu
Long summer days unequivocally stimulate, and short winter days inhibit reproduction in Siberian hamsters. By contrast, intermediate-duration day lengths (12.5-14 h long) either accelerate reproductive development or initiate regression of the reproductive apparatus. Which of these outcomes transpires depends on an animal's photoperiodic history, suggesting that hamsters must encode a representation of prior photoperiods. The duration of nocturnal melatonin secretion is the endocrine representation of day length, but nothing is known about how long it takes to establish photoperiodic histories or how long they endure. Hamsters exposed for 2 or more weeks to long summer day lengths acquired a long-day photoperiodic history that determined subsequent reproductive responses to intermediate-duration day lengths and melatonin signals. The memory for long-day lengths persisted in pinealectomized hamsters for 6.5 weeks, faded significantly after 13 weeks, and was functionally absent after 20 weeks. These findings indicate that hamsters are influenced only by relatively recent day lengths and melatonin signals and ignore earlier ones that might cause them to misinterpret the salience of current day lengths.
PMID: 10792054 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10899705&dopt=AbstractBiol Signals Recept 2000 May-Aug;9(3-4):203-12
Melatonin and biological rhythms.
Pevet P.
Neurobiologie des Fonctions Rythmiques et Saisonnieres, UMR 7518, CNRS, Universite Louis Pasteur, Strasbourg, France.
Circadian and seasonal rhythms are a fundamental feature of all living organisms. The functional mechanism involved is built around internal biological clock(s) and the hormone melatonin (Mel) is one of its critical components. Although numerous other sources have been identified (retina, harderian gland, gut), in vertebrates Mel is primarily produced by the pineal gland during the dark period of the light-dark cycle. This rhythmic Mel is generated directly by circadian clock(s). The Mel rhythm is thus an important efferent hormonal signal from the clock. The periodic secretion of Mel might thus be used as a circadian mediator of a system that can 'read' the message.The duration of the nocturnal Mel production is directly proportional to the length of the dark period. It is through these changes in duration that the brain integrates the photoperiodic information. In essence, the Mel rhythm appears to be an endocrine code of the environmental light-dark cycle conveying photic information that is used by organisms for both circadian and seasonal temporal organization. The major question arising from this effect of Mel concerns it precise mechanism of action. From the data reported in the present minireview, it appears that the photoneuroendocrine mechanism is not fundamentally different in vertebrates at least as far as the role of Mel is concerned. Copyright 2000 S. Karger AG, Basel
Publication Types:
- Review
- Review, Tutorial
PMID: 10899705 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11194713&dopt=AbstractJ Endocrinol Invest 2000 Dec;23(11):771-81
• • • Occupational and environmental agents as endocrine disruptors: experimental and human evidence.
Baccarelli A, Pesatori AC, Bertazzi PA.
Institute of Endocrine Sciences, Ospedale Maggiore, IRCCS, and EPOCA Research Center for Occupational, Clinical and Environmental Epidemiology, University of Milan, Italy. Andrea.Baccarelli@unimi.it
In the last few years great concern has arisen from the description of adverse endocrine effects of several occupational and environmental chemical agents on human and/or wildlife health. Such agents may exert their effects directly, specifically binding to hormone receptors, and/or indirectly, by altering the structure of endocrine glands and/or synthesis, release, transport, metabolism or action of endogenous hormones. Many studies have been focused on the outcomes of the exposure to those chemicals mimicking estrogenic or androgenic actions. Nonetheless, the disruption of other hormonal pathways is not negligible. This paper reviews the experimental and human evidence of the effects of occupational and environmental chemical agents on hypothalamus-pituitary unit, pineal gland, parathyroid and calcium metabolism and adrenal glands.
Publication Types:
- Review
- Review, Tutorial
PMID: 11194713 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11455326&dopt=AbstractNeuroendocrinol Lett 2000;21(1):31-34
Evidence of pineal endocrine hypofunction in autistic children.
Kulman G, Lissoni P, Rovelli F, Roselli MG, Brivio F, Sequeri P.
Division of Infant Neuropsychiatry, S.Gerardo Hospital, Monza (Milan), Italy.
OBJECTIVE: The pineal hormone melatonin (MLT) has been proven to play a fundamental physiological regulatory role on both biological and psychic functions and alterations of the light/dark circadian rhythm of MLT have been described in several chronic immunoinflammatory diseases and in psychic disorders. Aim of the present biological explanatory study was the evaluation of MLT circadian rhythm in autistic children, in order to preliminary assess the pineal endocrine function in the autistic syndrome.
METHODS: The study included 14 children suffering from classical infantile autism, who were investigated for the whole 24-hour circadian rhythm by collecting venous blood samples at 4-hour intervals. Serum levels of MLT were measured by the RIA method. The control group consisted of 20 age-matched healthy children.
RESULTS: No autistic patient showed a normal MLT circadian rhythm. Moreover, autistic children showed significantly lower mean concentrations of MLT, mainly during the dark phase of the day, with respect to the values observed in the controls.
CONCLUSION: The results of this preliminary study suggest the existence of a pineal endocrine hypofunction in autistic children, whose pathophysiological significance needs to be thoroughly investigated in successive clinical studies.
PMID: 11455326 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11133007&dopt=AbstractLife Sci 2000 Nov 3;67(24):2953-60
Effect of melatonin and pineal extracts on human ovarian and mammary tumor cells in a chemosensitivity assay.
Bartsch H, Buchberger A, Franz H, Bartsch C, Maidonis I, Mecke D, Bayer E.
University Women's Hospital, University of Tubingen, Germany. hella.bartsch@uni-tuebingen.de
Pinealectomy enhances tumor growth and metastatic spread in experimental animals. This effect is only in part due to melatonin since melatonin-free pineal extracts containing yet unidentified pineal substances have also shown tumor inhibiting activity. Despite numerous reports suggesting melatonin as a potential anti-cancer agent there have not been sufficient clinical trials to define the actual therapeutic potential of melatonin for the treatment of human cancers. To help fill this gap, we used a chemosensitivity assay designed to test the sensitivity of tumors from individual patients towards chemotherapeutic drugs for assessing the effect of melatonin and pineal extracts on primary human tumor cells. Primary cell cultures from seven ovarian and six mammary tumors were incubated with melatonin, the pineal extract YC05R (containing substances between 500 and 1000 daltons) and chemotherapeutic drugs. The pineal extract YC05R inhibited growth of all tumors in a dose-dependent manner. Physiological concentrations of melatonin (10(-8)-10(-10) M) inhibited the growth of one out of six mammary carcinomas in a dose-dependent manner. Primary cell cultures from three ovarian tumors were affected by melatonin in different ways, i.e., two were inhibited and one was slightly stimulated. There was no correlation between sensitivity towards melatonin and sex steroid receptor status, stage or grade of the tumor. It is concluded that,
1), melatonin may be an inhibitor of human mammary and ovarian carcinoma in individual cases and,
2), the pineal gland contains very active anti-tumor substances inhibiting both, the mammary and ovarian tumors, tested. These substances require chemical and biological identification.
PMID: 11133007 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11051776&dopt=AbstractRev Med Liege 2000 Aug;55(8):785-92
[Melatonin. I. Physiology of its secretion]
[Article in French]
Bruls E, Crasson M, Legros JJ.
Unite de Psychoneuroendocrinologie, Universite de Liege.
Melatonin is a hormone mainly secreted by the pineal gland during the dark phase of the light-dark cycle. The best known function of melatonin in mammals is to transmit information concerning light-dark cycles playing the role of an active neuroendocrine transducer of environmental information. Although melatonin circadian rhythm is endogenous, based on 25 hour cycles, it is modulated by light-dark cycle. During the day, the light signal is sent to the pineal gland through a special neuronal pathway and inhibits melatonin secretion. During the night, the last neuron of this pathway which is coming from the cervical ganglion superior releases nonadrenalin in the interstitium. Nonadrenalin stimulates melatonin synthesis through cAMP accumulation. Some factors other than light can also influence melatonin levels. Electromagnetic fields, age, male sex, Cushing syndrome, hypogonadotrophic hypogonadism, alcoholism seem to be associated with lower melatonin secretion. Female sex, hypergonadotrophic hypogonadism, sport and fasting seem to be linked to higher melatonin secretion. Some pathologies and drugs can modulate some steps of the neuroanatomic pathway of melatonin synthesis. Stress has no effect. The influence of weight and height is still investigated. Once released, melatonin can act on different organs through specific receptors (retina, supra-chiasmatic nucleus, hypophysis, brain, blood vessels, digestive tract, ovaries).
Publication Types:
- Review
- Review, Tutorial
PMID: 11051776 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11268363&dopt=AbstractAnn N Y Acad Sci 2000;917:376-86
Melatonin and its relation to the immune system and inflammation.
Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX.
Department of Cellular and Structural Biology, Mail Code 7762, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. reiter@uthscsa.edu
Melatonin (N-acetyl-5-methoxytryptamine) was initially thought to be produced exclusively in the pineal gland. Subsequently its synthesis was demonstrated in other organs, for example, the retinas, and very high concentrations of melatonin are found at other sites, for example, bone marrow cells and bile. The origin of the high level of melatonin in these locations has not been definitively established, but it is likely not exclusively of pineal origin. Melatonin has been shown to possess anti-inflammatory effects, among a number of actions. Melatonin reduces tissue destruction during inflammatory reactions by a number of means. Thus melatonin, by virtue of its ability to directly scavenge toxic free radicals, reduces macromolecular damage in all organs. The free radicals and reactive oxygen and nitrogen species known to be scavenged by melatonin include the highly toxic hydroxyl radical (.OH), peroxynitrite anion (ONOO-), and hypochlorous acid (HOCl), among others. These agents all contribute to the inflammatory response and associated tissue destruction. Additionally, melatonin has other means to lower the damage resulting from inflammation. Thus, it prevents the translocation of nuclear factor-kappa B (NF-kappa B) to the nucleus and its binding to DNA, thereby reducing the upregulation of a variety of proinflammatory cytokines, for example, interleukins and tumor neurosis factor-alpha. Finally, there is indirect evidence that melatonin inhibits the production of adhesion molecules that promote the sticking of leukocytes to endothelial cells. By this means melatonin attenuates transendothelial cell migration and edema, which contribute to tissue damage.
Publication Types:
- Review
- Review, Tutorial
PMID: 11268363 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11268355&dopt=AbstractAnn N Y Acad Sci 2000;917:29-37
Neurohormones and catecholamines as functional components of the bone marrow microenvironment.
Maestroni GJ.
Center for Experimental Pathology, Istituto Cantonale di Patologia, Locarno, Switzerland.
A variety of cytokines and growth factors exert a finely tuned control on the complex series of proliferative and differentiative events called hematopoiesis. Recent studies have shown that neuroendocrine and neural factors may also regulate hematopoiesis. In particular, besides its important immunoenhancing properties, the pineal neurohormone melatonin can also rescue hematopoiesis from the toxic effect of anti-cancer drugs via the action of T-helper cell novel opioid cytokines. In turn, these substances bind kappa-opioid receptors expressed in GM-CSF-activated macrophage-like stromal cells and seem to stimulate IL-1. Adrenergic agents can also affect hematopoiesis. We demonstrated that pre-B cells express alpha 1B-adrenoceptors (alpha 1B-AR) and that their activation by catecholamines results in suppressed myelopoiesis in vitro or protection in vivo against supralethal doses of carboplatin. Most recently, we found that alpha 1B-AR gene knockout mice show a deranged hematopoietic recovery after sublethal irradiation. Regeneration of pre-B cells (the cell type expressing alpha 1B-AR) and of erythrocytes was much faster in knockout than in wild-type mice. Most interesting, bone marrow cells can synthesize both melatonin and catecholamines. As far as melatonin is concerned, human and murine bone marrow cells contain and synthesize melatonin at a concentration that is three orders of magnitude higher than that normally found in serum. Catecholamines are also present in substantial amounts and originate both from nerve endings and bone marrow cells. These findings open interesting new perspectives and include hematology among the disciplines that would benefit from the integrative NIM approach.
Publication Types:
- Review
- Review, Tutorial
PMID: 11268355 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11032668&dopt=AbstractJ Comp Pathol 2000 Aug-Oct;123(2-3):146-51
Excretory plugs from the choroid plexus in the cerebrospinal fluid of dogs with neurological disease: possible role in the formation of corpora arenacea.
Garma-Avina A.
Department of Diagnostic and Field Services, Mississippi State University, Mississippi State, MS 39762, USA.
Cytological specimens of cerebrospinal fluid (CSF) from 13 (6.5%) of 200 dogs with various neurological diseases contained excretory plugs (EPs) originating from choroid plexus cells (ChPCs). The presence of EPs was not related to age, breed or sex, or to any particular neurological disease. EPs, which ranged from 3 to 25 microm in diameter, had a sharp outline and contained granular material. Many such bodies were also found within ChPCs of dogs without neurological disease, which were examined to determine the origin of EPs. The results suggest that EPs found in the CSF are excretory products originating in a small population of ChPCs, and that when they reach a certain size they are eliminated into the CSF. It is possible that they serve as cores around which corpora arenacea ("brain sand") are subsequently formed. Copyright 2000 Harcourt Publishers Ltd.
PMID: 11032668 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11268365&dopt=AbstractAnn N Y Acad Sci 2000;917:387-96
Gene regulation by melatonin.
Carlberg C.
Institut fur Physiologische Chemie I, Heinrich-Heine-Universitat Dusseldorf, Postfach 10 10 07, D-40001 Dusseldorf, Germany. carlberg@uni-duesseldorf.de
The physiological and neuroendocrine functions of the pineal gland hormone, melatonin, and its therapeutic potential critically depend on the understanding of its target sites and its mechanisms of action. This has progressed considerably in the last few years through the cloning of G protein-coupled seven-transmembrane melatonin receptors (Mel1a and Mel1b) as well as of nuclear receptors (RZR/ROR alpha and RZR beta) that are associated with melatonin signaling. The transcription factor RZR/ROR alpha appears to mediate a direct gene regulatory action of the hormone, and specific binding sites have been identified in promoter regions of a variety of genes, such as 5-lipoxygenase (5-LO), p21WAF1/CIP1, and bone sialoprotein (BSP). The membrane signaling pathway clearly shows higher ligand sensitivity than the nuclear signaling pathway, but details of its signal transduction cascade, and target genes are presently unknown. Membrane melatonin receptors are expressed mainly in the central nervous system, whereas RZR/ROR alpha is prominently expressed both in the periphery and the brain. The action of membrane melatonin receptors and their specific agonists have been associated with circadian rhythmicity, whereas direct effects of melatonin in the periphery, such as immunomodulation, cellular growth, and bone differentiation, mainly appear to be mediated by RZR/ROR alpha. It is hypothesized in this review that, in some cases, RZR/ROR alpha may be a primary target of membrane melatonin receptors.
Publication Types:
- Review
- Review, Tutorial
PMID: 11268365 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11268362&dopt=AbstractAnn N Y Acad Sci 2000;917:348-75
Feedsidewards: intermodulation (strictly) among time structures, chronomes, in and around us, and cosmo-vasculo-neuroimmunity. About ten-yearly changes: what Galileo missed and Schwabe found.
Halberg F, Cornelissen G, Katinas G, Watanabe Y, Otsuka K, Maggioni C, Perfetto F, Tarquini R, Schwartzkopff O, Bakken EE.
Halberg Chronobiology Center, University of Minnesota, 715 Mayo Building, Mayo Mail Code 8609, 420 Delaware St. S.E., Minneapolis, MN 55455, USA. halbe001@tc.umn.edu
The spectrum of biological rhythms is extended far beyond circadians, circannuals, and ultradians, such as 1.5-hourly melatonin and 8-hourly endothelin-1 (ET-1) rhythms by statistics of natality, growth, morbidity, and mortality, some covering decades or centuries on millions of individuals. These reveal infradian cycles to be aligned with half-weekly rhythms in ET-1, weekly and half-yearly ones in melatonin, and even longer--about 50-, about 20-, and about 10-year cycles found in birth statistics. About daily, weekly, yearly, and ten-yearly patterns are also found in mortality from myocardial infarctions; the 10-yearly ones are also in heart rate and its variability; in steroid excretion, an aspect of resistance, for example, to bacteria; and in the genetic changes of the bacteria themselves. Automatic physiological measurements cover years and, in one case, cover a decade; the latter reveal an about 10-year (circadecennial) cycle. ECGs, covering months beat-to-beat, reveal circaseptans, gaining prominence in response to magnetic storms or after coronary artery bypass grafting. A spectrum including cycles from fractions of 1 Hz to circasemicentennians is just one element in biological time structures, chronomes. Chaos, trends, and any unresolved variability are the second to fourth elements of chronomes. Intermodulations, feedsidewards, account for rhythmically and thus predictably recurring quantitive differences and even for opposite treatment effects of the same total dose(s) of (1) immunomodulators inhibiting or stimulating DNA labeling of bone in health or speeding up versus slowing down a malignant growth and thus shortening or lengthening survival time, or (2) raising or lowering blood pressure or heart rate in the vascular aspect of the body's defense. Latitude-dependent competing photic and nonphotic solar effects upon the pineal are gauged by alternating yearly (by daylight) and half-yearly (by night) signatures of circulating melatonin at middle latitudes and by half-yearly signatures at noon near the pole. These many (including novel near 10-yearly) changes, for example, in 17-ketosteroid excretion, heart rate, heart rate variability, and myocardial infarction in us and those galactic, solar, and geophysical ones around us have their own special signatures and contribute to a cosmo-vasculo-immunity and, if that fails, to a cosmo(immuno?) pathology.
Publication Types:
- Review
- Review, Tutorial
PMID: 11268362 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10981821&dopt=AbstractJ Pineal Res 2000 Sep;29(2):86-93
Melatonin inhibits apoptosis during early B-cell development in mouse bone marrow.
Yu Q, Miller SC, Osmond DG.
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
The pineal secretory product, melatonin, exerts a variety of effects on the immune system. Administration of melatonin stimulates cell-mediated immunity, particularly by inhibiting apoptosis among T lymphocytes in the thymus and inducing production of T-cell-derived cytokines. However, its possible effects on the humoral immune system are unclear. In the present study, we have examined whether melatonin may influence the in vivo development of B lymphocytes in mouse bone marrow, a process in which apoptosis is normally a prominent feature. Double immunofluorescence labeling and flow cytometry were used to quantitate phenotypically defined precursor B-cell and mature B-cell populations and their apoptotic rates in bone marrow of mice fed either melatonin-containing or control diet for 16 days from 9 wk of age. In short-term bone marrow cultures, the incidence of apoptosis among large pre-B cells, including cells expressing the lambda5 component of pre-B-cell receptor, was markedly reduced in melatonin-treated mice, associated with an increase in the absolute number of large pre-B cells in bone marrow. In contrast, apoptosis of earlier precursor B cells and mature B lymphocytes did not differ from control values. The results indicate that orally administered melatonin can substantially promote the survival of precursor B cells in mouse bone marrow. Melatonin treatment may thus boost the survival of newly formed B cells mediating humoral immunity.
PMID: 10981821 [PubMed - indexed for MEDLINE]
Full free report available at http://jcem.endojournals.org/cgi/content/full/85/6/2189J Clin Endocrinol Metab 2000 Jun;85(6):2189-96
Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia.
Zeitzer JM, Ayas NT, Shea SA, Brown R, Czeisler CA.
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.
PMID: 10852451 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10831154&dopt=AbstractJ Pineal Res 2000 May;28(4):193-202
Evidence for melatonin synthesis in mouse and human bone marrow cells.
Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM.
Istituto Cantonale di Patologia, Center for Experimental Pathology, Locarno, Switzerland. ario@bluewin.ch
Recently, it was demonstrated that inbred strains of mice have a clearcut circadian rhythm of pineal and serum melatonin. Moreover, it is known that melatonin is involved in many immunoregulatory functions. Among them, hematopoiesis is influenced by the action of melatonin via melatonin-induced opioids on kappa-opioid receptors, which are present on stromal bone marrow cells. Therefore, the present study was carried out to investigate the presence of melatonin in the bone marrow in which immunocompetent cells are generated. Specifically, we aimed at answering the following question: are bone marrow cells involved in melatonin synthesis? In the present study, we demonstrate that(1) bone marrow cells contain high concentrations of melatonin;
(2) bone marrow cells have a N-acetyltransferase activity and they express the mRNA encoding hydroxy-O-methyltransferase and
(3) bone marrow cells cultured for a prolonged period exhibited high levels of melatonin.Results presented here suggest that mouse and human bone marrow and bone marrow cells are capable of de novo synthesis of melatonin, which may have intracellular and or paracrine functions.
PMID: 10831154 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10773970&dopt=AbstractJoint Bone Spine 2000 Jan;67(1):62-4
Adolescent idiopathic scoliosis. Is low melatonin a cause?
Sadat-Ali M, al-Habdan I, al-Othman A.
Department of Orthopedic Surgery, King Fadh University Hospital, Al-Khobar, Saudi Arabia.
BACKGROUND: Although the cause of adolescent idiopathic scoliosis remains unclear, pinealectomy is followed by the development of scoliosis in chickens. Melatonin is the only hormone secreted by pineal gland.OBJECTIVE: To assess serum melatonin levels in adolescents with idiopathic scoliosis.
METHODS: Serum melatonin was assayed once, at 12:00 hours, in each of 20 adolescents with idiopathic scoliosis and 10 age-matched siblings. In the patient group, mean age was 14.3 years and the mean Cobb angle was 54.5 degrees (range, 20 degrees-110 degrees). Mean age in the control group was 14 years.
RESULTS: Serum melatonin was significantly lower in the patients (mean, 7.7 pg/mL; range, 4 to 13 pg/mL) than in the controls (mean, 29.9 pg/mL; range, 19.3 to 46 pg/mL) (P < 0.00001). The 12 surgically treated patients had a mean melatonin level of 8.1 pg/mL, versus 7.2 pg/mL in the eight other patients (nonsignificant P and regression coefficient values). Serum melatonin was not significantly correlated with the Cobb's angle (regression coefficient, 0.18; P < 0.44).
CONCLUSION: Our data suggest that serum melatonin levels may contribute to the pathogenesis of idiopathic scoliosis.
PMID: 10773970 [PubMed - indexed for MEDLINE]