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Pineal Gland Abstracts: 2004
Note: the following is a limited selection of abstracts available at PubMed, Science Direct, and Toxnet.
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2005 (Jan-June) |
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http://news.independent.co.uk/uk/health_medical/story.jsp?story=535733
The Independent (UK)
28 June 2004
Watching TV 'blocks sleep hormone in children'
By Philip Willan in Rome
Exposure to television can influence melatonin levels in children and possibly contribute to the premature onset of puberty, according to a study by scientists from the University of Florence.
The study found a 30 per cent increase in levels of the sleep-regulating hormone in children who had abstained from watching television for a week, the Rome daily La Repubblica reported yesterday.
The findings are based on a study of 74 children from the Tuscan town of Cavriglia who volunteered to forego television, video games and computers for a week last month in the interests of science. Aged between six and 12, the children normally watched an average of three hours' television a day. Urine samples taken at the beginning and end of the experiment showed a significant rise in melatonin levels, particularly among the younger children, by the end of the television-less week. As well as blacking out the video screens, parents were asked to reduce the intensity of artificial lighting in their homes during the experiment.
Melatonin is a hormone produced by the pineal gland, a pea-sized organ just above the middle of the brain. Exposure to light during the day inhibits its production, which normally begins around 9pm, with rising levels of melatonin in the blood making people feel sleepy. Scientists are less certain about the role of the hormone in regulating the onset of puberty, an issue the Florence researchers intend to pursue. In Western societies, the arrival of puberty has advanced by about a year since the 1950s, when television became common.
Neurosci Lett. 2004 Aug 26;367(1):79-84.
Vesicular inhibitory amino acid transporter is expressed in gamma-aminobutyric acid (GABA)-containing astrocytes in rat pineal glands.
Echigo N, Moriyama Y.
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tshushima-naka, Okayama 700-8530, Japan.
gamma-Aminobutyric acid (GABA) is an inhibitory amino acid and acts as an intercellular transmitter in the central nervous system and peripheral tissues. In pineal glands, GABA is supposed to be a paracrine-like modulator of secretion of melatonin, although its mode of action, especially the sites of GABA signal appearance, is unknown. Vesicular inhibitory amino acid transporter (VIAAT) is a potential marker for the GABAergic phenotype. Here we presented evidence that VIAAT is expressed in GFAP-expressing astrocytes and a subpopulation of OX42-expressing microglia, but not in pinealocytes in cultured cells of rat pineal glands. The VIAAT-expressing cells also exhibit GABA immunoreactivity. Essentially the same results were obtained for pineal glands. These results suggest that GABA is stored and secreted from astrocytes and a subpopulation of microglia in pineal glands.
PMID: 15308302 [PubMed - in process]
August 5, 2004
Register News, Burlington County NJ 08505
http://www.zwire.com/site/news.cfm?BRD=1091&dept_id=456077&newsid=12620973&PAG=461&rfi=9Golf tourney
Thursday, Aug. 19 — Friends of Jenna Golf Tournament will begin with a shotgun start at 12:30 p.m. at the Gambler Ridge Golf Club, Burlington Path Road, Cream Ridge. Cost is $95 per golfer and the deadline is Monday, Aug. 16. Hole sponsorship is available for $125.
Proceeds will help defray medical expenses for Fieldsboro/Bordentown resident Jenna Carroll, 15, who has been fighting an illness for about 18 months. She was recently diagnosed with a rare cancer (pineal) which affects the lining of her brain and spine. This illness has left her legally blind and as a result of her recent surgery she has to learn how to walk again. Jenna will go through chemotherapy and faces more surgeries.
Call Jean or Phil Horner at 298-1393 for details or e-mail mommadukes716@aol.com.
Neurosci Lett. 2004 Sep 30;368(3):243-8.
Influence of maternal pineal gland on the developmental pattern of neurokinin A (NKA) and substance P (SP) in male-rat-offspring: relationship to the season of the year.
Vazquez Moreno N, Debeljuk L, Diaz Rodriguez E, Fernandez Alvarez C, Diaz Lopez B.
Dpto. Biologia Funcional, Area Fisiologia, Facultad de Medicina, Universidad de Oviedo, C/Julian Claveria 6, 33006 Oviedo, Spain.
The present study examines the influence of maternal pineal gland on the frontal cortex, striatal and testicular concentrations of the tachykinins, neurokinin A (NKA) and substance P (SP). Control, pinealectomized (PIN-X) and PIN-X plus melatonin-treated (PIN-X + MEL) mother rats were prepared. Male offspring rats were studied at 21, 31 and 60 days of age, during the four seasons of the year. In control-offspring tachykinin concentrations in frontal cortex were found at their highest levels in 21-day-old rats with a moderate decrease up to 60 days of age. This developmental pattern was season-dependent, observed only during summer and fall. Maternal PIN-X or PIN-X + MEL resulted in alterations in the offspring, showing during spring and summer significantly higher concentrations (P < 0.01) and during fall significantly lower concentrations of tachykinins in the frontal cortex (P < 0.05, P < 0.01) as compared to control-offspring. The tachykinin concentration in the striatum of control-offspring showed no major modifications throughout the ages studied in the four seasons of the year. With very few exceptions, PIN-X- and PIN-X + MEL did not alter tachykinin concentrations in striatum. Testicular SP concentrations showed a decrease from 21 to 60 days of age. PIN-X or PIN-X + MEL only caused minor and inconsistent modifications in testicular SP levels. In conclusion, our data clearly indicate for the first time that the maternal pineal gland participates in the regulation of the postnatal tachykinin development in some areas of the central nervous system. This effect was more evident in the frontal cortex than in the striatum and testes.
PMID: 15364404 [PubMed - in process]
Life Sci. 2004 Sep 24;75(19):2291-302.
The profile of melatonin production in tumour-bearing rats.
Ferreira AC, Martins E Jr, Afeche SC, Cipolla-Neto J, Costa Rosa LF.
Laboratory of Metabolism, Department of Histology and Embryology, University of Sao Paulo, Brazil.
The pineal gland is involved in the regulation of tumour growth through the anticancer activity of melatonin, which presents immunomodulatory, anti-proliferative and anti-oxidant effects. In this study we measured melatonin content directly in the pineal gland, in an attempt to clarify the modulation of pineal melatonin secretory activity during tumour growth. Different groups of Walker 256 carcinosarcoma bearing rats were sacrificed at 12 different time points during 24h (12h:12h light/dark cycle) on different days during the tumour development (on the first, seventh and fourteenth day after tumour inoculation). Melatonin content in the pineal gland was determined by high-performance liquid chromatography with electrochemical detection. During tumour development the amount of melatonin secreted increased from 310.9 ng/mg of protein per day from control animals, to 918.1 ng/mg of protein per day 14 days after tumour implantation, and there were changes in the pineal production profile of melatonin. Cultured pineal glands obtained from tumour-bearing rats turned out to be less responsive to noradrenaline, suggesting the existence, in vivo, of putative factor(s) modulating pineal melatonin production. The results demonstrated that during tumour development there is a modification of pineal melatonin production daily profile, possibly contributing to cachexia, associated to changes in pineal gland response to noradrenaline stimulation.
PMID: 15350827 [PubMed - in process]
Note from FAN:
Definition of Cachexia - A profound and marked state of constitutional disorder, general ill health and malnutrition. The loss of body weight and muscle mass frequently seen in patients with advanced diseases. Synonyms: cachexy, wasting
Neuro Endocrinol Lett. 2004 Jun;25(3):173-5.
Precocious puberty associated with a pineal cyst: is it disinhibition of the hypothalamic-pituitary axis?
Dickerman RD, Stevens QE, Steide JA, Schneider SJ.Department of Neurosurgery, North Shore University-Long Island Jewish Medical Center, New Hyde Park, NY 11004, USA. drrdd@yahoo.com
Accelerated development of secondary sexual characteristics or sexual precocity is a well-known entity. Most authors recognize two groups of patients, those described as having central precocious puberty (CPP) and those with precocious pseudopuberty. CPP results from premature activation of the hypothalamic-pituitary-gonadal axis and pseudopuberty is caused by lesions that secrete gonadotropin-like substances or hormones. The onset of CPP is usually before age 8 in females and age 9 in males; however, there is contention that the age of onset is much earlier and also differs depending on the patients' race. Previously reported causes of CPP include intracranial neoplasm, infection, trauma, hydrocephalus and Angelman's syndrome. Pineal cysts are usually asymptomatic incidental findings, but have been associated with CPP. We present an interesting case of a patient with CPP and an associated pineal cyst. We review the literature on the pathogenesis of CPP and associated pineal cyst, the neuroendocrine relationship between the pineal gland and puberty and the neurosurgical role in these cases.
PMID: 15349080 [PubMed - in process]
Ann N Y Acad Sci. 2004 Dec;1035:216-30.
Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders.Lahiri DK, Chen D, Lahiri P, Rogers JT, Greig NH, Bondy S.
Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202. dlahiri@iupui.edu.
Melatonin is a hormone secreted by the pineal gland, mostly in the dark period of the light/dark cycle, with corresponding fluctuations reflected in the plasma melatonin levels. This hormone plays a critical role in the regulation of various neural and endocrine processes that are synchronized with daily change in photoperiod. Abnormal melatonin levels are associated with metabolic disturbances and other disorders. Melatonin potentially plays an important role in aging, prolongation of life span, and health in the aged individual. It may exert a beneficial action on neurodegenerative conditions in those with debilitating diseases. It interacts with metals and, in some cases, neutralizes their toxic effects. Levels of melatonin decrease with aging in mice. Its dietary supplementation has recently been shown to result in a significant rise in levels of endogenous melatonin in serum as well as all other tissue samples tested. The effects of dietary melatonin have been studied in the brain of mice with regard to nitric oxide synthase, synaptic proteins, and amyloid beta peptides (Abeta), which are involved in amyloid deposition and plaque formation in Alzheimer's disease (AD). Melatonin supplementation has no significant effect on cerebral cortical levels of nitric oxide synthase or synaptic proteins, such as synaptophysin and SNAP-25. Notably, however, elevated brain melatonin levels resulted in a significant reduction in levels of toxic cortical Abeta of both 40- and 42-amino-acid forms. Taken together, these results suggest that dietary melatonin supplementation may slow the neurodegenerative changes associated with brain aging and that the depletion of melatonin in the brain of aging mice may, in part, account for this adverse change.
PMID: 15681810 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15589268Front Neuroendocrinol. 2004 Sep;25(3-4):177-95.
Human pineal physiology and functional significance of melatonin.Macchi MM, Bruce JN.
New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 50, New York, NY 10032, United States.
Descriptions of the pineal gland date back to antiquity, but its functions in humans are still poorly understood. In both diurnal and nocturnal vertebrates, its main product, the hormone melatonin, is synthesized and released in rhythmic fashion, during the dark portion of the day-night cycle. Melatonin production is controlled by an endogenous circadian timing system and is also suppressed by light. In lower vertebrates, the pineal gland is photosensitive, and is the site of a self-sustaining circadian clock. In mammals, including humans, the gland has lost direct photosensitivity, but responds to light via a multisynaptic pathway that includes a subset of retinal ganglion cells containing the newly discovered photopigment, melanopsin. The mammalian pineal also shows circadian oscillations, but these damp out within a few days in the absence of input from the primary circadian pacemaker in the suprachiasmatic nuclei (SCN). The duration of the nocturnal melatonin secretory episode increases with nighttime duration, thereby providing an internal calendar that regulates seasonal cycles in reproduction and other functions in photoperiodic species. Although humans are not considered photoperiodic, the occurrence of seasonal affective disorder (SAD) and its successful treatment with light suggest that they have retained some photoperiodic responsiveness. In humans, exogenous melatonin has a soporific effect, but only when administered during the day or early evening, when endogenous levels are low. Some types of primary insomnia have been attributed to diminished melatonin production, particularly in the elderly, but evidence of a causal link is still inconclusive. Melatonin administration also has mild hypothermic and hypotensive effects. A role for the pineal in human reproduction was initially hypothesized on the basis of clinical observations on the effects of pineal tumors on sexual development. More recent data showing an association between endogenous melatonin levels and the onset of puberty, as well as observations of elevated melatonin levels in both men and women with hypogonadism and/or infertility are consistent with such a hypothesis, but a regulatory role of melatonin has yet to be established conclusively. A rapidly expanding literature attests to the involvement of melatonin in immune function, with high levels promoting and low levels suppressing a number of immune system parameters. The detection of melatonin receptors in various lymphoid organs and in lymphocytes suggests multiple mechanisms of action. Melatonin has been shown to be a powerful antioxidant, and has oncostatic properties as well, both direct and indirect, the latter mediated by its effects on reproductive hormones. Finally, there are reports of abnormal daily melatonin profiles in a number of psychiatric and neurological disorders, but the significance of such abnormalities is far from clear.
PMID: 15589268 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15580172Neuro Endocrinol Lett. 2004 Oct;25(5):368-72.
The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible interactions in the control of body temperature.Mazzoccoli G, Giuliani A, Carughi S, De Cata A, Puzzolante F, La Viola M, Urbano N, Perfetto F, Tarquini R.
Department of Internal Medicine, Regional General Hospital Casa Sollievo della Sofferenza, Opera di Padre Pio da Pietrelcina, Cappuccini Av., 71013 S.Giovanni Rotondo (FG), Italy.
OBJECTIVE: Melatonin plays a role in the regulation of biological rhythms, body temperature presents circadian variations with lower levels during nighttime, when melatonin levels are very high, and thyroid hormones influence shiver independent thermogenesis. We have investigated on possible interactions between the hypothalamic-pituitary-thyroid axis and melatonin in the control of body temperature in humans.
METHODS: Peripheral blood samples for thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free-thyroxine (FT4), melatonin levels determination and body temperature measurements were obtained every four hours for 24-hours starting at 0600 h in a controlled temperature and light-dark environment from ten healthy males, aged 38-65 (mean age +/-s.e. 57.4+/-3.03, mean body mass index +/-s.e. 25.5+/-0.75). We calculated fractional variation and correlation on single time point hormone serum levels and tested whether the time-qualified data series showed consistent pattern of circadian variation.
RESULTS: A statistically significant difference was evidenced for the fractional variation of daytime TSH serum levels (0600 h-1000 h vs. 1000 h-1400 h, p=0.01, 1000 h-1400 h vs. 1400 h-1800 h, p=0.0001, 1400 h-1800 h vs. 1800 h-2200 h, p=0.001) and for the fractional variation of FT4 serum levels at 1800 h-2200 h vs. 2200 h-0200 h (p=0.02). FT4 serum levels correlated positively with TRH serum levels at 1000 h (r=0.67, P=0.03) and at 1400 h (r=0.63, p=0.04), negatively with TSH serum levels at 2200 h (r=-0.67, p=0.03), negatively with melatonin serum levels at 2200 h (r=-0.64, p=0.04) and at 0200 h (r=-0.73, p=0.01). TRH serum levels correlated positively with TSH serum levels at 0200 h (r=0.65, p=0.04) and at 0600 h (r=0.64, p=0.04). Body temperature correlated positively with FT4 serum levels at 1000 h (r=0.63, p=0.04) and negatively with melatonin serum levels at 0200 h (r=-0.64, p=0.04). A clear circadian rhythm was validated for body temperature (with acrophase in the morning) and melatonin, TRH and TSH secretion (with acrophase at night), while FT4 serum level changes presented ultradian periodicity (with acrophase in the morning).
CONCLUSION: Changes of TSH serum levels are smaller and those of FT4 are greater at night, when melatonin levels are higher, so that the response of anterior pituitary to hypothalamic TRH and of thyroid to hypophyseal TSH may be influenced by the pineal hormone that may modulate the hypothalamic-pituitary-thyroid axis function and influence the circadian rhythm of body temperature.
PMID: 15580172 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15597771J Neurosurg. 2004 Dec;101(6):1061-4.
Primary extraskeletal osteosarcoma in the pineal region. Case report.
Saesue P, Chankaew E, Chawalparit O, Na Ayudhya NS, Muangsomboon S, Sangruchi T.
Division of Neurosurgery, Department of Surgery, Siriraj Hospital, Mahidol University, Bangkok, Thailand. sipas@mucc.mahidol.ac.th
Primary extraskeletal osteosarcoma occurring in the brain parenchyma is distinctly uncommon, with only five cases having been reported. The authors describe the case of a 45-year-old man who presented with progressive headache and diplopia. Computerized tomography scanning and magnetic resonance imaging results revealed a pineal region tumor with obstructive hydrocephalus. The patient underwent partial resection of the tumor. The histological examination showed large pleomorphic tumor cells embedded in osteoid matrix. Immunohistochemical analysis was negative for various antibodies and thus excluded a glial, germ cell, epithelial, and lymphoid tumor origin. Only vimentin showed strong positivity in most of the tumor cells. Ultrastructurally, the tumor cells were rich in dilated rough endoplasmic reticula. Clear zones between tumor cells and osteoid matrix were observed. The osteoid matrix was made up of small collagen fibrils and hydroxyapatite deposits. The tumor was not attached to the bone structure of the skull. These findings are consistent with the features of extraskeletal osteosarcoma. Data from complete medical and radiological studies excluded a metastatic origin for this tumor. Partial resection and postoperative radiotherapy had provided tumor control at 11 months after the onset of symptoms. This is the first reported case of a primary extraskeletal osteosarcoma occurring in the pineal region.
PMID: 15597771 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15605771Vopr Onkol. 2004;50(4):454-8.
[Diethylstilbestrol-induced uterine sarcoma in mice][Article in Russian]
[No authors listed]
Female mice of CBA strain received diethylstilbestrol (DES) 1 g body weight intraperitoneally. High incidence of histiocytic uterine sarcoma was observed in parents (25%), first generation (F1), descendants (10.9%), and generation F2m (through F1 males mated with females in control) (17.8%). Morphologically, tumor cells examined through light and electron microscopy were referred to as histiocyte-like elements. Half of the animals had metastases in the liver, kidneys, lungs, spleen, pineal and adrenal glands and stomach. The development of tumors in generation F2m, which was not exposed to DES, might be accounted for by "transgeneration" carcinogenesis, i.e. passage of carcinogenic effect through a generation.
PMID: 15605771 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15581421Curr Drug Targets CNS Neurol Disord. 2004 Dec;3(6):515-33.
The neuronal cytoskeleton as a potential therapeutical target in neurodegenerative diseases and schizophrenia.Benitez-King G, Ramirez-Rodriguez G, Ortiz L, Meza I.
Instituto Nacional de Psiquiatria, Departamento de Neurofarmacologia, Subdireccion de Investigaciones Clinicas, Mexico, D.F., Mexico. bekin@imp.edu.mx.
The cytoskeleton plays a key role in maintaining the highly asymmetrical shape and structural polarity of neurons that are essential for neuronal physiology. Cytoskeletal reorganization plays a key role in neuritogenesis. In neurodegenerative diseases, the cytoskeleton is abnormally assembled and impairment of neurotransmission occurs. In Alzheimer's disease, abundant amyloid plaques and neurofibrillary tangles constitute the two major neuropathologic alterations present in the brain. Neurofibrillary tangles are formed of paired helical filaments consisting nearly entirely of the microtubule-associated protein tau. Under normal conditions tau binds to microtubules, stabilizing neuron structure and integrity. Hyperphosphorylation of tau is assumed to be the cause of formation of paired helical filaments. Another example of cytoskeletal abnormalities present in neurodegenerative diseases are the Lewy bodies considered as cytopathologic markers of Parkinson's disease. Lewy bodies are constituted of tubulin, MAP1, and MAP2. Neuronal shape, loss of dendrites and spines, as well as irregular distribution of neuronal elongations occur in specific brain areas of schizophrenic patients. Increase in non-phosphorylated MAP2 and MAP1B at hippocampus has been suggested as responsible for somatodendritic and cytoarchitectural abnormalities found in schizophrenia. In addition, neurofibrillary tangles are more frequent among schizophrenic patients who received pharmacologic antipsychotic treatment. Cumulative evidence suggests that neurodegenerative diseases and psychiatric illnesses are associated with cytoskeletal alterations in neurons that, in turn, loose synaptic connectivity and the ability to transmit incoming axonal information to the somatodendritic domain. We will review evidence supporting that the neuronal cytoskeleton is disrupted in neurodegenerative and some psychiatric diseases, and therefore could be a target for drug therapy. In addition, current data indicating that melatonin, a hormone secreted by the pineal gland, promotes neuritogenesis through cytoskeletal rearrangements and in addition to the potential therapeutic use of melatonin in neurodegenerative diseases will be discussed.
PMID: 15581421 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15582681Pharmacol Biochem Behav. 2004 Dec;79(4):733-7.
Melatonin inhibits the development of tolerance to U-50,488H analgesia via benzodiazepine-GABA(A)ergic mechanisms.Dhanaraj E, Nemmani KV, Ramarao P.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, S.A.S. Nagar-160 062 (Pb), India.
Melatonin, a primary secretory product of pineal gland, is known to produce many of its pharmacological actions via benzodiazepine-gamma-aminobutyric acid(A) (GABA(A))ergic mechanisms. Recently, we showed that benzodiazepine-GABA(A)ergic mechanisms play an important role in U-50,488H (U50) analgesia and its tolerance. Hence, in the present study, the effect of melatonin on U50 analgesia and its tolerance was investigated. Furthermore, the possible role of benzodiazepine-GABA(A)ergic mechanisms in the actions of melatonin on U50 analgesia was investigated. All experiments were performed using the radiant tail-flick test for mice. Melatonin [0.2, 1 and 5 mg/kg, intraperitoneal (i.p.)] neither produced analgesia nor affected the acute U50 (40 mg/kg, i.p.) analgesia. Tolerance to U50 analgesia was induced by administering U50 (40 mg/kg, i.p.) twice daily over 6 days. Treatment with melatonin (1 and 5 mg/kg, i.p) 15 min prior to each dose of U50 inhibited the development of tolerance, whereas a low dose of melatonin (0.2 mg/kg, i.p.) did not. The inhibition of U50 tolerance by melatonin was reversed by the chronic treatment with flumazenil (0.1 mg/kg), a benzodiazepine receptor antagonist and picrotoxin (1 mg/kg), a GABA(A)-gated chloride channel blocker. Flumazenil and picrotoxin neither affected tail-flick latencies nor altered acute U50 analgesia and its tolerance. Interestingly, chronic 6-day melatonin treatment in a vehicle (U50-naive) group did not alter U50 analgesia measured on day 7. Together, these findings suggest that melatonin interferes with the neural mechanisms involved in the development of tolerance to U50 analgesia. The inhibition of U50 tolerance by melatonin was reversed by flumazenil and picrotoxin treatment, suggesting that benzodiazepine-GABA(A)ergic mechanisms play an important role in the development of tolerance to U50 analgesia and that melatonin inhibits the development of U50 tolerance via benzodiazepine-GABA(A)ergic mechanisms.
PMID: 15582681 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15616152Drug Metab Dispos. 2004 Dec 22; [Epub ahead of print]
METABOLISM OF MELATONIN BY HUMAN CYTOCHROMES P450.Ma X, Idle JR, Krausz KW, Gonzalez FJ.
National Cancer Institute.
In humans, the pineal hormone melatonin (MEL) is principally metabolized to 6-hydroxymelatonin (6-HMEL), which is further conjugated with sulfate and excreted in urine. MEL O-demethylation represents a minor reaction. The exact role of individual human cytochromes P450 in these pathways has not been established. We used a panel of 11 recombinant human P450 isozymes to investigate for the first time the 6-hydroxylation and O-demethylation of MEL. CYP1A1, CYP1A2 and CYP1B1 all 6-hydroxylated MEL, with CYP2C19 playing a minor role. These reactions were NADPH-dependent. CYP2C19, and to some extent CYP1A2, O-demethylated MEL. The Km (microM) and Vmax (kcat, pmol min-1 pmol-1 P450) for 6-hydroxylation were estimated as 19.2+/-2.01, 6.46+/-0.22 (CYP1A1); 25.9+/-2.47, 10.6+/-0.32 (CYP1A2); 30.9+/-3.76, 5.31+/-0.21 (CYP1B1). These findings confirm the suggestion of others that CYP1A2 is probably the foremost hepatic P450 in the 6-hydroxylation of MEL and a single report that CYP1A1 is also able to mediate this reaction. However, this is the first time that CYP1B1 has been shown to 6-hydroxylate MEL. The IC50 for the CYP1B1 selective inhibitor TMS was estimated to be 30 nM for MEL 6-hydroxylation by recombinant human CYP1B1. Comparison of brain homogenates from wild-type and cyp1b1-null mice, revealed that MEL 6-hydroxylation was clearly mediated to a significant degree by CYP1B1. CYP1B1 is not expressed in the liver but has a ubiquitous extrahepatic distribution and is found at high levels in tissues that also accumulate either MEL or 6-HMEL, such as intestine and cerebral cortex, where it may assist in regulating levels of MEL and 6-HMEL.
PMID: 15616152 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15608359J Physiol Pharmacol. 2004 Jul;55 Suppl 2:33-46.
Modulation of pancreatic enzyme secretion by melatonin and its precursor: L-tryptophan. Role of CCK and afferent nerves.Leja-Szpak A, Jaworek J, Nawrot-Porabka K, Palonek M, Mitis-Musiol M, Dembinski A, Konturek SJ, Pawlik WW.
Dept Med Physiol Faculty of Health Care, Jagiellonian University Collegium Medicum, Cracow, Poland. mpjawore@cyf-kr.edu.pl.
Melatonin, a pineal hormone, is also produced in the gastrointestinal tract. Melatonin receptors have been detected in the stomach, intestine and pancreas. This indole inhibits insulin secretion but its role in the physiological modulation of exocrine pancreatic function is yet unknown. The aim of this study was to evaluate the pancreatic secretory effect of melatonin and its precursor; L-tryptophan given intraduodenally (i.d.) to the conscious rats with intact or capsaicin deactivated sensory nerves. CCK(1) receptor antagonist; tarazepide, was used in the part of the study to determine the involvement of CCK in the secretory effects of melatonin. The secretory studies were performed on awaken rats surgically equipped with silicone catheters, one of them was inserted into pancreato-biliary duct, the other one - into duodenum. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) were administered i.d. Samples of pancreatic juice were collected in 15 minutes aliquots. Tarazepide (2,5 mg/kg i.p.) was given to the rats 15 min prior to the administration of melatonin or L-tryptophan. Neurotoxic dose of capsaicin (100 mg/kg s.c.) was used to deactivate afferent nerves and thus to assess the role of these nerves in the melatonin-induced pancreatic enzyme secretion. Administration of melatonin (1, 5 or 25 mg/kg i.d.) or L-tryptophan (10, 50 or 250 mg/kg i.d.) significantly increased pancreatic amylase outputs. Deactivation of sensory nerves by capsaicin or administration of CCK(1) - receptor antagonist; tarazepide, reversed the stimulatory effects of melatonin or L-tryptophan on pancreatic secretory function. Administration of melatonin or its amino-acid precursor to the rats resulted in the significant and dose-dependent rises of melatonin and CCK plasma levels. We conclude that melatonin or its precursor; L-tryptophan stimulates pancreatic enzyme secretion via stimulation of CCK release and activation of duodeno-pancreatic reflexes.
PMID: 15608359 [PubMed - in process]
Note: full free paper is available by going to: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15550511Endocrinology. 2004 Nov 18; [Epub ahead of print]
DAILY VARIATIONS IN TYPE II IODOTHYRONINE DEIODINASE ACTIVITY IN THE RAT BRAIN AS CONTROLLED BY THE BIOLOGICAL CLOCK.Kalsbeek A, Buijs RM, van Schaik R, Kaptein E, Visser TJ, Zandieh Doulabi B, Fliers E.
Netherlands Institute for Brain Research (A.K, R.L.V.S.), Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands; Department of Internal Medicine III (E.K., T.J.V.), Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands; Academic Medical Center (B.Z.D, E.F.), Department of Endocrinology and Metabolism, F5-171, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Type II deiodinase (D2) plays a key role in regulating thyroid-hormone dependent processes in, among others, the central nervous system (CNS), by accelerating the intracellular conversion of thyroxine (T4) into active thyroid hormone, T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid (HPT) axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS, as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland, as well as in hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all 4 tissues studied. The main effect of the knock-out of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the HPT-axis.
PMID: 15550511 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15556393Comp Biochem Physiol A Mol Integr Physiol. 2004 Nov;139(3):365-9.
Seasonal changes in brain melatonin concentration in the three-spined stickleback (Gasterosteus aculeatus): towards an endocrine calendar.Sokolowska E, Kalamarz H, Kulczykowska E.
Department of Genetics and Marine Biotechnology, Institute of Oceanology of Polish Academy of Sciences, sw. Wojciecha 5 Str., 81-347 Gdynia, Poland.
Pineal organ and its hormone melatonin (N-acetyl-5-methoxytryptamine) is likely involved in timing and synchronisation of many internal processes, such as reproduction, with annual changes in environmental cues, i.e., photoperiod and water temperature. The seasonal changes in melatonin profile in stickleback brains related to the following reproductive phases were examined, and the link between melatonin concentrations and the stages of spawning cycle was analysed. Two wild populations of sticklebacks were exposed to annual environmental changes in their natural habitats. Brains, gonads, kidneys and livers were collected over 2 years. Melatonin was measured using RIA and the indices, gonadosomatic (GSI), nephrosomatic (NSI) and hepatosomatic (HSI), were calculated. The role of melatonin, as a component of internal calendar engaged in the control of seasonal breeding in this species, is discussed. The extremely high melatonin levels observed in early spring (March) and autumn (October) seem to mark out a time frame for spawning in sticklebacks. The seasonal pattern of melatonin production and identified development stages of gonads suggests the potential inhibitory effect of the hormone on stickleback reproduction in shortening photoperiod and stimulatory effect in lengthening photoperiod.
PMID: 15556393 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15559508Adv Gerontol. 2004;14:105-13.
[The influence of substances revealing geroprotective of spontaneous carcinogenesis in mice][Article in Russian]
[No authors listed]
The review presents the results of experimental studies conducted by the author. CBA, SHR, HER-2/neu and SAM mice revealed inhibition of age-related alterations in estrus function and spontaneous tumour development and showed life span extension under the influence of the pineal gland hormone Melatonin, synthetic peptide bioregulator Epitalon, delta-sleep-inducing peptide Deltaran, enterosorbent Aqualen and succinic acid containing preparation Neuronol (Noogam). The observed effect depended on the dose and conditions of administration, as well as genetic predisposition of the particular mice strains to tumour development.
PMID: 15559508 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15562014J Clin Endocrinol Metab. 2004 Nov 23; [Epub ahead of print]
Human lymphocyte-synthesized melatonin is involved in the regulation of the IL-2/IL-2 receptor system.Carrillo-Vico A, Lardone PJ, Fernandez-Santos JM, Martin-Lacave I, Calvo JR, Karasek M, Guerrero JM.
Department of Medical Biochemistry and Molecular Biology and Department of Normal and Pathological Cytology and Histology, The University of Seville School of Medicine and Virgen
Macarena Hospital, Seville, Spain. Laboratory of Electron Microscopy, Chair of Pathology, Medical University of Lodz, Lodz, Poland.
Since melatonin was first isolated in 1958 up to the last few years, this substance was considered a hormone exclusive to the pineal gland. Although melatonin has lately been identified in a large number of extrapineal sites, its potential biological actions have not yet been studied. This paper shows that human lymphocyte-synthesized melatonin plays a crucial role modulating IL-2/IL-2 receptor system, since when blocking melatonin biosynthesis by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine, both IL-2 and IL-2 receptor levels fell, restoring them by adding exogenous melatonin. Moreover, we demonstrated this endogenous melatonin interfered with the exogenous melatonin effect on IL-2 production. Melatonin exerted these effects by a receptor-mediated action mechanism, because both IL-2 and IL-2 receptor expressions significantly decreased when lymphocytes were incubated in the presence of the specific membrane and/or nuclear melatonin receptor antagonists, luzindole and/or CGP 55644, respectively. Finally, we made the real significance of the membrane melatonin receptors in this process clear, so prostaglandin E2-induced inhibition on IL-2 production increased when we blocked the membrane receptors using luzindole. In conclusion, these data show that endogenous melatonin is an essential part for an accurate response of human lymphocytes through the modulation of IL-2/IL-2 receptor system.
PMID: 15562014 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15547321Biogerontology. 2004 Oct;5(5):339-345.
Pineal graft in old rats improves erythrocyte resistance to peroxyl radical-induced hemolysis.Moroni F, Marcheselli F, Recchioni R, Fattoretti P, Bertoni-Freddari C.
INRCA Research Department, Centre of Cytology, Via Birarelli 8, Italy.
Pineal graft from young to old rats was performed and red blood cell hemolysis, induced by the water-soluble radical initiator 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), was evaluated 6 months after graft. Pineal graft modified the hemolysis curve kinetic profile in grafted rats versus age-matched controls, the 50% hemolysis time as well as the lag time were longer, whereas the maximal amount of hemolysis was lower, and it occurred over a longer period of time. Thiobarbituric acid reactive substances production was lower in pineal-grafted rats than in controls and the age-related decrease of erythrocyte membrane fluidity was prevented by pineal graft. The present findings support an important physiological role of pineal gland in preventing age-related alterations of erythrocyte membranes and suggest a possible antioxidant action of melatonin.
PMID: 15547321 [PubMed - as supplied by publisher]
Micron , Volume 35, Issue 8 , December 2004, Pages 655-670
Bizarre alterations of the morphology of pineal synaptic bodies under constant light and an evaluation of suitable 3D-reconstruction softwareHolger Jastrow (a), Dirk Schmanke (b) and Jörg Weinert (c)
a Department of Anatomy, University of Mainz, Becherweg 13, D-55128, Mainz, Germany
b University Clinic Central Network Group, Langenbeckstr. 1, D-55101, Mainz, Germany
c ConVis Medizinische Datenverarbeitung GmbH & Co. KG, Robert-Bosch-Str. 23, 55129, Mainz, GermanyReceived 10 May 2004; Revised 7 June 2004; accepted 8 June 2004. Available online 2 July 2004.
Abstract - Three dimensional (3D) reconstruction and modelling software was evaluated to find a procedure suitable for visualization of small subcellular structures in transmission electron microscope images. The method applied in this study demonstrates bizarre alterations of the structure of synaptic bodies (SBs) in pinealocytes of the guinea-pig pineal gland caused by constant illumination. It can, in general, be used for any 3D reconstruction from serial sections.
Pineal glands of five guinea-pigs (two kept under a LD cycle of 12:12 h; three kept in constant light, for 4 months) were investigated. SBs consist of an electron-dense centre with attached vesicles. Under normal lighting conditions most SBs are flat plates (about 35 nm in thickness), which eventually may be bent. The proteins comprising the molecular basis of SBs, mainly RIBEYE A and B are polymerised in a regular manner in these plates. This is not the case in other SBs, which appear as spheres or irregular lumps. SBs lie in groups in which usually some of the plates are arranged in parallel arrays
Constant illumination caused different changes in morphology: many of the SBs lie in ‘paired fields’, i.e. appear in groups attached to the cell membranes of two pinealocytes directly opposite to each other. Some of the SBs in such groups are strongly bent, showing blebs and irregular thickened areas, others seem to aggregate and show inclusions of cytoplasm. Further goblet-like, shield-like and other bizarre forms of SBs occurred and the relative number of spheroid and lump-like SBs increased. Protrusions on larger SBs suggest detachment or fusion of SB material to a greater extent than in the control animals. There is a reduction of areas in which the polymerisation of the SB proteins remains well ordered, i.e. where the typical thickness of 35 nm is maintained. It remains unclear why this polymerisation pattern is only partly affected by constant light.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15450952Biochem Pharmacol. 2004 Nov 1;68(9):1869-78.
Oxidative DNA damage induced by a melatonin metabolite, 6-hydroxymelatonin, via a unique non-o-quinone type of redox cycle.Sakano K, Oikawa S, Hiraku Y, Kawanishi S.
Department of Environmental and Molecular Medicine, Mie University School of Medicine, Mie 5148507, Japan.
Melatonin, an indolic pineal hormone, is produced primarily at night in mammals and is important in controlling biological rhythms. Although melatonin is known to be effective as a free radical scavenger and has an anti-cancer effect, carcinogenic properties have also been reported. In relation to its carcinogenic potential, we have examined whether 6-hydroxymelatonin, a major melatonin metabolite, can induce DNA damage in the presence of metal ion using [(32)P]-5'-end-labeled DNA fragments obtained from genes relevant to human cancer. 6-Hydroxymelatonin induced site-specific DNA damage in the presence of Cu(II). Formamidopyrimidine-DNA glycosylase treatment induced cleavage sites mainly at G residues of the 5'-TG-3' sequence, whereas piperidine treatment induced cleavage sites at T mainly of 5'-TG-3'. Interestingly, 6-hydroxymelatonin strongly damaged G and C of the 5'-ACG-3' sequence complementary to codon 273 of the p53 gene. These results suggest that 6-hydroxymelatonin can cause double-base lesions. DNA damage was inhibited by both catalase and bathocuproine, Cu(I)-specific stabilizer, suggesting that reactive species derived from the reaction of H(2)O(2) with Cu(I) participate in DNA damage. Cytochrome P450 reductase efficiently enhanced 6-hydroxymelatonin-induced oxidative DNA damage and oxygen consumption, suggesting the formation of redox cycle. It is noteworthy that 6-hydroxymelatonin can efficiently induce DNA damage via non-o-quinone type of redox cycle. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in calf thymus DNA was significantly increased by 6-hydroxymelatonin in the presence of Cu(II). Furthermore, 6-hydroxymelatonin significantly increased the formation of 8-oxodG in human leukemia cell line HL-60 but not in HP100, a hydrogen peroxide (H(2)O(2))-resistant cell line derived from HL-60. The 6-hydroxymelatonin-induced 8-oxodG formation in HL-60 cells significantly decreased by the addition of bathocuproine or o-phenanthroline. Therefore, it is concluded that melatonin may exhibit carcinogenic potential through oxidative DNA damage by its metabolite.PMID: 15450952 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15530547Acta Histochem. 2004 Nov 25;106(5):331-336.
Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats.Sahna E, Parlakpinar H, Vardi N, Cigremis Y, Acet A.
Department of Pharmacology, Faculty of Medicine, Firat University, Elazig, Turkey.
Previous observations demonstrated that physiological levels of melatonin, the pineal secretory product, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects of pinealectomy and administration of exogenous melatonin on liver tissue in rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, reduced glutathione (GSH) levels and malondialdehyde (MDA) levels. Rats were divided into three groups (10 rats in each group): control (non-Px), Px+vehicle and Px+melatonin (4mg/kg given daily intraperitoneally for 10 days). Liver GSH levels were significantly lower in Px rats than in the control group. Melatonin administration significantly increased GSH levels (p<0.05). Px caused a significant increase in MDA levels as compared with the control group and melatonin administration to Px rats significantly reduced MDA levels in the liver (p<0.05). Sinusoidal dilatation to a varying degree developed in all Px rats. Severity of mononuclear cell infiltration and sinusoidal congestion were lower in Px+melatonin group than in the Px group. These findings suggest that a significant increase in oxidative and structural changes occur in rat livers after pinealectomy, which can be diminished by melatonin treatment.
PMID: 15530547 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15378522Prostate. 2004 Sep 17 [Epub ahead of print]
Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism.Sainz RM, Mayo JC, Tan DX, Leon J, Manchester L, Reiter RJ.
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas.
BACKGROUND: Melatonin, the main secretory product of the pineal gland, inhibits the growth of several types of cancer cells. Melatonin limits human prostate cancer cell growth by a mechanism which involves the regulation of androgen receptor function but it is not clear whether other mechanisms may also be involved.
METHODS: Time-course and dose-dependent studies were performed using androgen-dependent (LNCaP) and independent (PC3) prostate cancer cells. Cell number, cell viability, and cell cycle progression were studied. Neuroendocrine differentiation of these cells was evaluated by studying morphological and biochemical markers. Finally, molecular mechanisms including the participation of melatonin membrane receptors, intracellular cAMP levels, and the PKA signal transduction pathway were also analyzed. RESULTS: Melatonin treatment dramatically reduced the number of prostate cancer cells and stopped cell cycle progression in both LNCaP and PC3 cells. In addition, it induced cellular differentiation as indicated by obvious morphological changes and neuroendocrine biochemical parameters. The role of melatonin in cellular proliferation and differentiation of prostate cancer cells is not mediated by its membrane receptors nor related to PKA activation.
CONCLUSIONS: The treatment of prostate cancer cells with pharmacological concentrations of melatonin influences not only androgen-sensitive but also androgen-insensitive epithelial prostate cancer cells. Cell differentiation promoted by melatonin is not mediated by PKA activation although it increases, in a transitory manner, intracellular cAMP levels. Melatonin markedly influences the proliferative status of prostate cancer cells. These effects should be evaluated thoroughly since melatonin levels are diminished in aged individuals when prostate cancer typically occurs. Copyright 2004 Wiley-Liss, Inc.PMID: 15378522 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15384069J Comp Neurol. 2004 Oct 25;478(4):379.
Distribution of transcription factor inducible cyclicAMP early repressor (ICER) in rodent brain and pituitary.Kell CA, Dehghani F, Wicht H, Molina CA, Korf HW, Stehle JH.
Dr. Senckenbergische Anatomie, Institute of Anatomy II, University of Frankfurt, 60590 Frankfurt, Germany.
In morphogenetic dynamics of neurons, and in adaptive physiology of brain function, transcription factors of the cyclicAMP signaling pathway, such as activator cyclicAMP responsive element binding protein (CREB) and inhibitor inducible cyclicAMP early repressor (ICER), play an important role. In particular, the presence of the transcription factor ICER in neurons or neuroendocrine cells suggests the need for the gating of an up-regulated gene expression. Little is known, however, about the natural distribution of the inhibitory transcription factor ICER. We, therefore, mapped the rodent brain and pituitary for an ICER immunoreaction and found a nuclear staining for this transcription factor. ICER-positive glial cells were found throughout the brain. ICER-positive neurons were found in sensory input centers, like the olfactory bulb, or sensory brain stem nuclei, and in hypothalamic nuclei involved in central neuroendocrine control. In addition, neuroendocrine/endocrine transducers, like the pituitary and the pineal gland showed a high basal presence of ICER. Our data show that a basic ICER level is required by many cell systems and can be seen as an anticipatory and/or a protective measure in systems with superior reactive dynamics.
PMID: 15384069 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15379450Acta Vet Hung. 2004;52(3):361-7.
Effect of melatonin on biochemical variables of the blood in dairy cows.
Darul K, Kruczynska H.
Department of Animal Nutrition and Feed Management, August Cieszkowski Agricultural University, ul Wolynska 33, 60-637 Poznan, Poland.
In order to examine the effect of exogenous melatonin on selected biochemical variables of the blood in ruminants, dairy cows were given the pineal gland hormone in the dose of 0.1 mg/kg body weight. One and four hours after melatonin administration blood samples were collected from the cows in the control and the treated group in order to determine the levels of glucose, insulin, total cholesterol, triglycerides, free fatty acids, as well as the activities of alanine and aspartate aminotransferase. The pineal gland hormone caused a significant increase in the levels of total cholesterol and triglycerides, slight increases in glucose and insulin levels, and a significant decrease in the concentration of free fatty acids. Melatonin did not exert an effect on the activity of liver enzymes.
PMID: 15379450 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15375761Histol Histopathol. 2004 Oct;19(4):1187-92.
Melatonin-like immunoreactivity in the pineal gland of the cow: an immunohistochemical study.Carvajal JC, Gomez-Esteban MB, Carbajo S, Munoz-Barragan L.
Department of Human Anatomy and Histology, Faculty of Medicine, University of Salamanca, Spain.
With a view to checking the presence of melatonin in the pineal gland of the cow, in the present work we used six adult animals, ranging in age from one to six years, which were sacrificed at dawn. Sections of 6 micro m thickness of Bouin-fixed and paraffin-embedded pineal glands were incubated in an anti-melatonin serum, which was provided by the Institute for Molecular and Cellular Recognition, Gunma University, Maebshi, Japan. After incubation and successive washings in PBS, some of the sections were treated with the avidin-biotin-peroxidase complex (ABC) technique using antisera from Sigma, and developed with the method of Graham and Karnovsky (which employs 3,3'-diaminobenzidine and H2O2 as developer). Other sections were incubated in a goat-anti-rabbit IgG (H+L) bound to fluorochrome Cy5 for immunofluorescence studies. An intense reaction for melatonin was observed in the cytoplasm but not in the nucleus of melatonin secreting pinealocytes located in peripheral and intermediate zones of the pineal gland. Immunoabsorption of the antimelatonin primary antibody with melatonin at a dilution of 10 mM per 0.1 ml of serum prevented the reaction, as happened when any of the antisera used in the procedure were used. Immunoabsorption of anti-melatonin serum with different amounts of bovine albumin (ranging between 1/5 to 1/50) failed to inhibit the immunoreactivity. When a bovine anti-albumin antibody was employed, working with the above methods, no immunoreaction was detected. Our data suggest that the pinealocytes of cows sacrificed at dawn contain immunoreactive melatonin.
PMID: 15375761 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15447706Headache. 2004 Oct;44(9):929-30.
Headaches and pineal cyst: a (more than) coincidental relationship?Peres MF, Zukerman E, Porto PP, Brandt RA.
Pineal cysts are common findings in neuroimaging studies. The cysts are more frequent in women in their third decade of life. Pineal cysts can be symptomatic, headache is the most common symptom. The pineal gland has important physiological implications in humans, but little is known about the impact of pineal cysts in human physiology. We report 5 headache patients with pineal cyst, 4 women, 1 man, mean age 37.6, mean cyst diameter 10.1 mm. Two patients had migraine without aura, 1 migraine with aura, 1 chronic migraine, and 1 hemicrania continua. Three patients had strictly unilateral headaches. We hypothesize pineal cysts may be not incidental in headache patients, inducing an abnormal melatonin secretion.
PMID: 15447706 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15465605J Neuroimmunol. 2004 Nov;156(1-2):146-52.
Neutrophils as a specific target for melatonin and kynuramines: effects on cytokine release.Silva SO, Rodrigues MR, Ximenes VF, Bueno-da-Silva AE, Amarante-Mendes GP, Campa A.
Departamento de Analises Clinicas e Toxicologicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo CEP 05508-900, SP, Brazil.
A growing body of evidence suggests that the pineal hormone, melatonin, has immunomodulatory properties, although very little is known about its effect on leukocytes. Therefore, we aimed to investigate the effect of melatonin and its oxidation product N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) on cytokine production by neutrophils and peripheral blood mononuclear cells (PBMCs). AFMK (0.001-1 mM) inhibits the lipopolysaccharide (LPS)-mediated production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) more efficiently in neutrophils than PBMCs. Moreover, the inhibitory activity of AFMK is stronger than that of melatonin. Interestingly, monocytes efficiently oxidize melatonin to AFMK. We conclude that neutrophils are one of the main targets for melatonin and that at least part of the effects described for melatonin on immune cells may be due to its oxidation product, AFMK. We also consider that the oxidation of melatonin may be an important event in the cross-talking between neutrophils and monocytes.
PMID: 15465605 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15449681Arkh Patol. 2004 Jul-Aug;66(4):13-6.
[Human epiphyseal concrements in schizophrenia]
[Article in Russian]
[No authors listed]
The epiphysis is a gland containing firm extracellular bodies (brain sand) the number of which increases with age. Microscopy and roentgen microtomography showed that in some cases of schizophrenia the amount of brain sand decreases. In parallel, cytoplasm of pinealocytes appears to contain concrements of a new type--irregular hollow spheres of 0.1-1.5 microm in size. They may contain fluoride. Typical hydroxyapatite retaining organic stroma may dissolve starting from the center both in health and schizophrenia.
PMID: 15449681 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15455095Bull Exp Biol Med. 2004 Jun;137(6):597-600.
Effects of pineal peptides on circadian dynamics of spermatogonia proliferation in albino rats.
[Article in English, Russian]
Arav VI, Sych VF, Zheleznyak EV, Slesarev SM.
Department of Common Biology, Ul'yanovsk State University. bio@ulsu.ru
Mitotic index of type B spermatogonia in intact animals is characterized by a circadian rhythm. Mitotic index increased and its circadian rhythm disappeared after pinealectomy. Treatment with Epithalamin for 14 days restored the circadian rhythm. The circadian biorhythm of spermatogonia proliferation suggests the presence of circadian rhythm of spermatogenesis in general and its regulation by the pineal gland.
PMID: 15455095 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15469089Sheng Li Ke Xue Jin Zhan. 2004 Jul;35(3):210-4.
[Advances in study on molecular mechanism of circadian clock in pineal gland]
[Article in Chinese]
Wang GQ, Tong J.
Department of Physiology, Medical School, Soochow University, Suzhou 215007.
The pineal gland functions as a central circadian oscillator in a variety of nonmammalian vertebrates. More recently, clock genes such as Per, Cry, Clock, and Bmal have been found in a variety of vertebrate clock structures including the avian pineal gland. The profiles of the temporal change of the clock gene expression in the avian pineal gland are more similar to those in the mammalian suprachiasmatic nucleus (SCN) of the hypothalamus. Avian pineal gland and mammalian SCN seem to share a fundamental molecular framework of the clock oscillator composed of a transcription/translation-based autoregulatory feedback loop. Some products of the clock genes serve as positive or negative regulators influencing the clock oscillation. The circadian time-keeping mechanism is also involved in several post-translational events. The above-mentioned processes play a quite important role in the stability of the oscillator and/or the photic-input pathway for entrainment of the clock.
PMID: 15469089 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15357659J Pineal Res. 2004 Oct;37(3):153-60.
Protective effect of N-acetyl-serotonin on the nonenzymatic lipid peroxidation in rat testicular microsomes and mitochondria.
Gavazza MB, Catala A.
Catedra de Bioquimica, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina.
N-acetyl-serotonin, the immediate precursor of melatonin in the tryptophan metabolic pathway in the pineal gland, has been reported to be an antioxidant. The aim of this study was to test the in vitro protective effect of N-acetyl-serotonin on the ascorbate-Fe(++) induced lipid peroxidation of polyunsaturated fatty acids (PUFAs) located in testis microsomes and mitochondria. We assayed increasing concentrations (0-10 mm) of N-acetyl-serotonin in testis microsomes and (0-1 mm) of N-acetyl-serotonin in testis mitochondria. Control experiments were performed by incubating microsomal and mitochondrial membranes with N-acetyl-serotonin in the absence of lipid peroxidation-inducing drugs. Special attention was paid to the changes produced on the highly PUFAs C20:4 n6 and C22:5 n6. The light emission (chemiluminescence) used as a marker of lipid peroxidation was similar in both organelles when the control and peroxidized groups were compared. N-acetyl-serotonin reduced lipid peroxidation in testicular microsomes or mitochondria for both C20:4 n6 and C22:5 n6. Both long chain PUFAs were protected when N-acetyl-serotonin was incorporated either into microsomes or mitochondria. The N-acetyl-serotonin concentration required to inhibit by approximately 70% lipid peroxidation process was 10 mm in microsomes and between 0.50 and 1 mm in mitochondria. IC 50 values calculated from the inhibition curve of N-acetyl-serotonin on the chemiluminescence rates were higher in microsomes (4.50 mm) than in mitochondria (0.25 mm). In these experimental conditions, N-acetyl-serotonin was about 18 times more potent in testicular mitochondria in inhibiting the oxidative processes than it was in testicular microsomes. These results suggest that the protective role of N-acetyl-serotonin in preserving the long PUFAs may be related to its ability to reduce lipid peroxidation.
PMID: 15357659 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15357143Rev Neurosci. 2004;15(3):209-30.
Genetic aspects of melatonin biology.
Anisimov SV, Popovic N.
Section for Neuronal Survival, Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, Lund, Sweden. Sergey.Anisimov@mphy.lu.se
For decades, the important physiological roles of the pineal hormone have inspired scientific investigations. Research efforts have generated a broad amount of information relevant to various genetic aspects of melatonin biology. Nevertheless, our understanding of the effect of genetic factors upon melatonin biosynthesis and the mechanisms of gene expression regulation by melatonin in target tissues is far from complete. The present review makes an effort to summarize and systematize the existing information on the subject, sequentially discussing
(i) the effect of genetic factors upon melatonin biosynthesis,
(ii) melatonin receptor expression profiles, and
(iii) the effect of melatonin upon expression of genes in target tissues.PMID: 15357143 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15356035J Clin Endocrinol Metab. 2004 Sep;89(9):4388-90.
Increase in 6-Hydroxymelatonin Excretion in Humans during Ascent to High Altitudes.Frisch H, Waldhauser F, Waldhor T, Mullner-Eidenbock A, Neupane P, Schweitzer K.
Department of Pediatrics, University Hospital Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. herwig.frisch@meduniwien.ac.at
Melatonin (MLT), the pineal gland hormone involved in the regulation of circadian rhythms, shows characteristic diurnal variation. Its physiological role in humans is not clear. Exposure to high altitudes may disrupt the circadian rhythm and lead to various endocrine changes. MLT in humans has not been studied under these conditions. Urinary 6-hydroxy-MLT sulfate (aMT6s) excretion was analyzed during the day (0700-2200 h) and night (2200-0700 h) phases. A cohort of 33 healthy volunteers, aged 19-65 yr, was studied during an ascent to a high altitude in the Himalayas on three occasions (at a lower altitude, at 3400 m, and after reaching maximal altitudes of 5600-6100 m). aMT6s excretion during the daytime remained unchanged during exposure to high altitudes. As expected, nocturnal values were higher than diurnal values at each point in time. However, there was a significant increase in nocturnal MLT excretion after the ascent to high altitudes. Ascent to high altitudes is associated with increased nocturnal excretion of aMT6s. The mechanism and physiological significance of this MLT increase are unclear.
PMID: 15356035 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15352385J Physiol Biochem. 2004 Mar;60(1):61-72.
Physiological and metabolic functions of melatonin.Barrenetxe J, Delagrange P, Martinez JA.
Dpt. Physiology and Nutrition, University of Navarra, C/Irunlarrea, s/n, Pamplona, Spain.
Melatonin is a lipophilic hormone, mainly produced and secreted at night by the pineal gland. Melatonin synthesis is under the control of postganglionic sympathetic fibers that innervates the pineal gland. Melatonin acts via high affinity G protein-coupled membrane receptors. To date, three different receptor subtypes have been identified in mammals: MT1 (Mel 1a) and MT2 (Mel 1b) and a putative binding site called MT3. The chronobiotic properties of the hormone for resynchronization of sleep and circadian rhythms disturbances has been demonstrated both in animal models or in clinical trials. Several other physiological effects of melatonin in different peripheral tissues have been described in the past years. In this way, it has been demonstrated that the hormone is involved in the regulation of seasonal reproduction, body weight and energy balance. This contribution has been focused to review some of the physiological functions of melatonin as well as the role of the hormone in the regulation of energy balance and its possible involvement in the development of obesity.
PMID: 15352385 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15352165J Cell Biochem. 2004 Sep 1;93(1):83-92.
Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: Possible immune cell activation.Simko M, Mattsson MO.
Division of Environmental Physiology, Institute of Cell Biology and Biosystems Technology, University of Rostock, Albert-Einstein-Strasse 3, D-18059 Rostock, Germany.
There is presently an intense discussion if electromagnetic field (EMF) exposure has consequences for human health. This include exposure to structures and appliances that emit in the extremely low frequency (ELF) range of the electromagnetic spectrum, as well as emission coming from communication devices using the radiofrequency part of the spectrum. Biological effects of such exposures have been noted frequently, although the implication for specific health effects is not that clear. The basic interaction mechanism(s) between such fields and living matter is unknown. Numerous hypotheses have been suggested, although none is convincingly supported by experimental data. Various cellular components, processes, and systems can be affected by EMF exposure. Since it is unlikely that EMF can induce DNA damage directly, most studies have examined EMF effects on the cell membrane level, general and specific gene expression, and signal transduction pathways. In addition, a large number of studies have been performed regarding cell proliferation, cell cycle regulation, cell differentiation, metabolism, and various physiological characteristics of cells. Although 50/60 Hz EMF do not directly lead to genotoxic effects, it is possible that certain cellular processes altered by exposure to EMF indirectly affect the structure of DNA causing strand breaks and other chromosomal aberrations. The aim of this article is to present a hypothesis of a possible initial cellular event affected by exposure to ELF EMF, an event which is compatible with the multitude of effects observed after exposure. Based on an extensive literature review, we suggest that ELF EMF exposure is able to perform such activation by means of increasing levels of free radicals. Such a general activation is compatible with the diverse nature of observed effects. Free radicals are intermediates in natural processes like mitochondrial metabolism and are also a key feature of phagocytosis. Free radical release is inducible by ionizing radiation or phorbol ester treatment, both leading to genomic instability. EMF might be a stimulus to induce an "activated state" of the cell such as phagocytosis, which then enhances the release of free radicals, in turn leading to genotoxic events. We envisage that EMF exposure can cause both acute and chronic effects that are mediated by increased free radical levels:
(1) Direct activation of, for example macrophages (or other cells) by short-term exposure to EMF leads to phagocytosis (or other cell specific responses) and consequently, free radical production. This pathway may be utilized to positively influence certain aspects of the immune response, and could be useful for specific therapeutic applications.
(2) EMF-induced macrophage (cell) activation includes direct stimulation of free radical production.
(3) An increase in the lifetime of free radicals by EMF leads to persistently elevated free radical concentrations. In general, reactions in which radicals are involved become more frequent, increasing the possibility of DNA damage.
(4) Long-term EMF exposure leads to a chronically increased level of free radicals, subsequently causing an inhibition of the effects of the pineal gland hormone melatonin.
Taken together, these EMF induced reactions could lead to a higher incidence of DNA damage and therefore, to an increased risk of tumour development. While the effects on melatonin and the extension of the lifetime of radicals can explain the link between EMF exposure and the incidence of for example leukaemia, the two additional mechanisms described here specifically for mouse macrophages, can explain the possible correlation between immune cell system stimulation and EMF exposure. Copyright 2004 Wiley-Liss, Inc.PMID: 15352165 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15344912J Neuroendocrinol. 2004 Sep;16(9):741-9.
Activation of arylalkylamine N-acetyltransferase by phorbol esters in bovine pinealocytes suggests a novel regulatory pathway in melatonin synthesis.
Schomerus C, Laedtke E, Korf HW.
Dr Senckenbergische Anatomie, Institut fur Anatomie II, Johann Wolfgang Goethe-Universitat Frankfurt, Frankfurt, Germany.
In all mammalian species investigated, noradrenaline activates a beta-adrenoceptor/cAMP/protein kinase A-dependent mechanism to switch on arylalkylamine N-acetyltransferase and melatonin biosynthesis in the pineal gland. Other compounds which are known to influence the melatonin-generating system are phorbol esters. The effect of phorbol esters on regulation of melatonin synthesis has been mainly investigated in rat pinealocytes. In these cells, phorbol esters do not increase cAMP levels and arylalkylamine N-acetyltransferase on their own; however, phorbol esters potentiate the effects on cAMP and AANAT activity induced upon beta-adrenoceptor stimulation. In the present study, we investigated the effect of phorbol esters on the regulation of melatonin synthesis in bovine pinealocytes. We show that, in these cells, the phorbol esters 4beta-phorbol 12-myristate 13-acetate (PMA) or phorbol 12,13-dibutyrate have a direct stimulatory effect and induced 4-10-fold increases in AANAT protein levels, AANAT activity and melatonin production. The extent of these effects was similar to those induced by noradrenaline. Notably, responses to PMA were not accompanied by increases in cAMP levels. Northern blot analysis showed that Aanat mRNA levels did not change upon PMA treatment indicating that phorbol esters control AANAT at a post-transcriptional level. The effects on AANAT and melatonin production were reduced by use of protein kinase C inhibitors, but not by blockade of the cyclic AMP/protein kinase A pathway. Our results point towards a novel mechanism in the regulation of melatonin production that is cAMP-independent and involves protein kinase C. The study is of particular interest because regulation of melatonin biosynthesis in bovines may resemble that in primates more closely than that in rodents.
PMID: 15344912 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15357664J Pineal Res. 2004 Oct;37(3):193-7.
Melatonin increases cell proliferation in the dentate gyrus of maternally separated rats.Kim MJ, Kim HK, Kim BS, Yim SV.
Department of Obesity Management, Graduate School of Obesity Science, Dongduk Women's University, Seoul, South Korea.
Melatonin in mammals, produced by the pineal gland and elsewhere, has shown antioxidant and neuroprotective properties in neuronal cells. We investigated whether melatonin would increase newly born cells (cell proliferation) in the dentate gyrus of maternally separated rats. To examine the effect of melatonin on cell proliferation of the dentate gyrus in maternally separated rats, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was performed. Rat pups were separated from their mothers and socially isolated on postnatal day 14. Melatonin (10 mg/kg, i.p.) and BrdU (50 mg/kg, i.p.) were given to them for 7 days. The number of BrdU-positive cells was significantly increased in the dentate gyrus of maternally separated pups with melatonin administration (P < 0.001). In addition, the expression of glucocorticoid receptor was significantly decreased in the dentate gyrus compared with maternally separated pups not given melatonin (P < 0.001). This is the first report that melatonin increases cell proliferation in the dentate gyrus of maternally separated rats.
PMID: 15357664 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15357831Pigment Cell Res. 2004 Oct;17(5):454-60.
Melatonin, melatonin receptors and melanophores: a moving story.Sugden D, Davidson K, Hough KA, Teh MT.
Division of Reproductive Health, Endocrinology and Development, School of Biomedical Sciences, Kings College London, London, UK.
Melatonin (5-methoxy N-acetyltryptamine) is a hormone synthesized and released from the pineal gland at night, which acts on specific high affinity G-protein coupled receptors to regulate various aspects of physiology and behaviour, including circadian and seasonal responses, and some retinal, cardiovascular and immunological functions. In amphibians, such as Xenopus laevis, another role of melatonin is in the control of skin coloration through an action on melanin-containing pigment granules (melanosomes) in melanophores. In these cells, very low concentrations of melatonin activate the Mel(1c) receptor subtype triggering movement of granules toward the cell centre thus lightening skin colour. Mel(1c) receptor activation reduces intracellular cAMP via a pertussis toxin-sensitive inhibitory G-protein (Gi), but how this and other intracellular signals regulate pigment movement is not yet fully understood. However, melanophores have proven an excellent model for the study of the molecular mechanisms which coordinate intracellular transport. Melanosome transport is reversible and involves both actin- (myosin V) and microtubule-dependent (kinesin II and dynein) motors. Melanosomes retain both kinesin and dynein during anterograde and retrograde transport, but the myosin V motor seems to be recruited to melanosomes during dispersion, where it assists kinesin II in dominating dynein thus driving net dispersion. Recent work suggests an important role for dynactin in coordinating the activity of the opposing microtubule motors. The melanophore pigment aggregation response has also played a vital role in the ongoing effort to devise specific melatonin receptor antagonists. Much of what has been learnt about the parts of the melatonin molecule required for receptor binding and activation has come from detailed structure-activity data using novel melatonin ligands. Work aiming to devise ligands specific for the distinct melatonin receptor subtypes stands poised to deliver selective agonists and antagonists which will be valuable tools in understanding the role of this enigmatic hormone in health and disease.
PMID: 15357831 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15325001Med Hypotheses. 2004;63(4):588-96.
Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue.Pauley SM.
P.O. Box 3759, Ketchum, ID 83340, USA.
The hypothesis that the suppression of melatonin (MLT) by exposure to light at night (LAN) may be one reason for the higher rates of breast and colorectal cancers in the developed world deserves more attention. The literature supports raising this subject for awareness as a growing public health issue. Evidence now exists that indirectly links exposures to LAN to human breast and colorectal cancers in shift workers. The hypothesis begs an even larger question: has medical science overlooked the suppression of MLT by LAN as a contributor to the overall incidence of cancer? The indirect linkage of breast cancer to LAN is further supported by laboratory rat experiments by David E. Blask and colleagues. Experiments involved the implanting of human MCF-7 breast cancer cell xenografts into the groins of rats and measurements were made of cancer cell growth rates, the uptake of linoleic acid (LA), and MLT levels. One group of implanted rats were placed in light-dark (12L:12D) and a second group in light-light (12L:12L) environments. Constant light suppressed MLT, increased cancer cell growth rates, and increased LA uptake into cancer cells. The opposite was seen in the light-dark group. The proposed mechanism is the suppression of nocturnal MLT by exposure to LAN and subsequent lack of protection by MLT on cancer cell receptor sites which allows the uptake of LA which in turn enhances the growth of cancer cells. MLT is a protective, oncostatic hormone and strong antioxidant having evolved in all plants and animals over the millennia. In vertebrates, MLT is normally produced by the pineal gland during the early morning hours of darkness, even in nocturnal animals, and is suppressed by exposure to LAN. Daily entrainment of the human circadian clock is important for good human health. These studies suggest that the proper use and color of indoor and outdoor lighting is important to the health of both humans and ecosystems. Lighting fixtures should be designed to minimize interference with normal circadian rhythms in plants and animals. New discoveries on blue-light-sensitive retinal ganglion cell light receptors that control the circadian clock and how those receptors relate to today's modern high intensity discharge (HID) lamps are discussed. There is a brief discussion of circadian rhythms and light pollution. With the precautionary principle in mind, practical suggestions are offered for better indoor and outdoor lighting practices designed to safeguard human health.
PMID: 15325001 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15311999Physiol Res. 2004;53(4):403-8.
Pinealectomy increases and exogenous melatonin decreases leptin production in rat anterior pituitary cells: an immunohistochemical study.Kus I, Sarsilmaz M, Colakoglu N, Kukne A, Ozen OA, Yilmaz B, Kelestimur H.
Department of Physiology, Medical School, Firat University, 23119 Elazig, Turkey. e-mail: hkelestimur@firat.edu.tr
Melatonin, the main hormone of the pineal gland, informs the body about the environmental light and darkness regimen, which in turn contributes to the photoperiodic adaptation of several physiological functions. Leptin, the hormone secreted mainly by adipocytes and some other tissues including the pituitary, informs the brain about the mass of adipose tissue, which plays an important role in energy homeostasis. Melatonin has been shown to decrease circulating leptin levels. It is currently not known whether melatonin has an effect on leptin synthesis in the pituitary. The aim of this study was to immunohistochemically examine the effects of pinealectomy and administration of melatonin on leptin production in the rat anterior pituitary. The pituitary samples obtained from 18 male Wistar rats including sham-pinealectomized, pinealectomized and melatonin-injected pinealectomized groups were immunohistochemically evaluated. Immunostaining of leptin was moderate (3+) in sham-pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in melatonin-treated pinealectomized rats, respectively. The present results indicate that pinealectomy induces leptin secretion in anterior pituitary cells, and this increase of leptin synthesis can be prevented by administration of melatonin. Thus, melatonin seems to have both physiological and pharmacological effects on leptin production in the anterior pituitary of male rats.
PMID: 15311999 [PubMed - in process]
http://www.fluoridealert.org/pesticides/pineal.aug.20.2004.york.pa.htmAugust 20, 2004
News article published by the York Dispatch (Pennsylvania)
Relief from darkness. Brain surgery at 13.
By Megan Shirey
A 15 year old girl "suffered from a symptomatic pineal brain lesion since age 9. She had severe headaches and vision problems and was very sensitive to light ..."
http://www.fluoridealert.org/pesticides/pineal.nih.aug.12.2004.htmAugust 12, 2004.
Press Release from US National Institutes of Health
Pineal Gland Evolved To Improve Vision, According To Theory By NICHD Scientist. Theory May Increase Understanding of Eye Disease, Sleep Disorders.
The pineal gland — which regulates the cycles of sleep and waking — appears to have evolved as an indirect way to improve vision, by keeping toxic compounds away from the eye, according to a new theory by a researcher at the National Institute of Child Health and Human Development at the National Institutes of Health. The theory has implications for understanding macular degeneration, a condition causing vision loss in people age 60 and older. The theory is described in the August Journal of Biological Rhythms and represents the work of David Klein, Ph.D., Chief of NICHD's Section on Neuroendocrinology. Dr. Klein studies melatonin, the pineal hormone that regulates sleep and wake cycles ... Briefly, the theory holds that melatonin was at first a kind of cellular garbage, a by-product created in cells of the eye when normally toxic substances were rendered harmless. Roughly 500 million years ago, however, the ancestors of today's animals became dependent on melatonin as a signal of darkness. As the need for greater quantities of melatonin grew, the pineal gland developed as a structure separate from the eyes, to keep the toxic substances needed to make melatonin away from sensitive eye tissue ...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15302263