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Journal Article 2002; 23(3): 231-237 PubMed PMID: 12080284 Citation  Keywords:  Altitude, Animals, Animals, Newborn, Hypoxia:pathology, Male, Mitochondria:physiology, Organ Size, Rats, Rats, Wistar, Testis:chemistry, Testosterone:analysis,.   

OBJECTIVE: To investigate the effects of continued hypoxia on postnatal development of the rat testis.

DESIGN: Wistar rats were exposed to simulated hypoxia from birth to postnatal day (PND) 45. Testosterone (T) in the plasma and the testis was measured in rats at PND 3, 7, 14, 21, 28, 35 and 45 respectively. Testis histology and cellular ultrastructure were studied.

RESULTS: a) Hypoxia induced a significant arrest of testes weight gain after PND 28; b) T release was significantly attenuated after PND 21; c) Alterations in histology and cellular ultrastructure were found in the testis, showing the swelling of testis interstitium and the enlargement of mitochondria in Leydig cells.

CONCLUSION: Postnatal hypoxia stress alters testis development both in terms of function and structure, especially at the critical age of gonadal development....

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Clinical Trial 2002; 23(3): 213-217 PubMed PMID: 12080281 Citation  Keywords:  Adult, Body Temperature:drug effects, Circadian Rhythm:drug effects, Humans, Male, Melatonin:blood, Pineal Gland:drug effects, Pyridoxine:administration & dosage, Sleep:drug effects,.   

OBJECTIVES: To determine pineal response to pyridoxine in normal men.

MATERIAL AND METHODS: Twelve healthy men were given orally pyridoxine (100 mg) or placebo at 1700h. Serum melatonin levels were determined every 30 minutes with simultaneous measurement of core body temperature between 1700h to 0300h. Polysomnographic sleep recordings were performed between 1800h to 2000h.

RESULTS: Serum melatonin levels after both placebo and pyridoxine showed a nocturnal rise occurring at 22:10+/-1:22h and 22:24+/-1:09h, respectively. The melatonin onset, peak, mean and area under the curve (AUC) values after pyridoxine (3.2+/-1.6 pg/ml, 47.2+/-22.6 pg/ml, 31.5+/-11.0 pg/ml and 173.5+/-138.4 pg/ml x min, respectively) were similar to the values after placebo administration (4.7+/-1.6 pg/ml, 53.9+/-26.0 pg/ml, 37.2+/-2.8 pg/ml and 205.3+/-137.8 pg/ml x min, respectively). CBT revealed a significant nocturnal decline but without significant difference between pyridoxine and placebo. Sleep amount and architecture were similar after the two treatments.

CONCLUSIONS: In adult man, the oral administration of 100 mg-pyridoxine during the evening hours has no effect on melatonin secretion nor does it alter CBT or sleep quality....

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Journal Article 2002; 23(Suppl 1): 73-78 PubMed PMID: 12019356 Citation  Keywords:  Animals, Antioxidants:metabolism, Humans, Melatonin:physiology, Pineal Gland:drug effects, Thyroid Gland:growth & development, Thyroid Hormones:pharmacology,.   

: This review briefly summarizes the published data on relationships observed between melatonin - the main pineal hormone, and the thyroid gland. The prevailing part of the survey is devoted to thyroid growth processes and function. A large experimental evidence exists suggesting the inhibitory action of melatonin on thyroid growth and function; this effect has been revealed by using different experimental models: by chronic and short-term melatonin administration in vivo, by light restriction, which is known to increase the activity of the pineal gland, by pinealectomy, etc., as well as by employing the in vitro conditions. Thus, much information has been accumulated, indicating - in experimental conditions - a mutual relationship between the pineal gland and the thyroid. The confirmation of these relations in clinical studies in humans meets numerous difficulties, resulting - among others - from the fact that, nowadays, human beings, as well as certain animal species, used in experimental studies, have been living far away from their natural and original habitat. It makes almost impossible to compare the results obtained in particular studies performed in different species, on the pineal-thyroid interrelationship....

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Journal Article 2002; 23(Suppl 1): 67-72 PubMed PMID: 12019355 Citation  Keywords:  Animals, Antioxidants:pharmacology, Cell Division:drug effects, Cell Membrane:drug effects, Cells, Cultured, Chickens:physiology, Colforsin:pharmacology, Cyclic AMP:metabolism, Lymphocytes:drug effects, Male, Melatonin:pharmacology, Phytohemagglutinins:ph.   

OBJECTIVES: Time-dependent melatonin effects on chicken lymphocyte proliferation in vitro and the involvement of cAMP in melatonin signal transduction were examined.

MATERIALS AND METHODS: Splenocytes and peripheral blood mononuclear cells (PBMC) were cultured in vitro in the presence of melatonin, phytohemagglutinin, luzindole, dibutyrylcAMP (dbcAMP), forskolin and vasoactive intestine peptide (VIP). Proliferation was measured by [(3)H]-thymidine incorporation in cultures carried out for 24, 36, 48 and 72 h. Cyclic AMP formation was assessed by radioimmunoassay in cells incubated for 30 min. or 24 h.

RESULTS: Melatonin stimulated the spontaneous proliferation in short-term (36 and 48 h) splenocyte cultures and had no effect in 72 h cultures. It inhibited mitogen-stimulated proliferation already in 24 h cultures and this effect was observed regardless of the time of the culture. Both melatonin effects were antagonized by luzindole - membrane-bound melatonin receptor antagonist. Forskolin and dbcAMP caused a significant inhibition of proliferation of splenocytes and PBMC cultured for 24 or 72 h, respectively. Melatonin inhibited the cAMP formation (30 min. of incubation) stimulated by adenosine cyclase activators - forskolin and VIP, but added alone failed to affect the cAMP concentration. In mitogen-stimulated splenocytes cultured for 24 h Mel caused an increase in cAMP correlated with the inhibition of cell proliferation.

CONCLUSIONS: Melatonin effects on chicken splenocytes appears time- and activation-dependent: in short-term cultures it stimulates spontaneous and inhibits mitogen-activated proliferation, probably via membrane-bound, luzindole-sensitive melatonin receptors. Incubation with melatonin for 30 min. inhibits cAMP formation, but in 24 h cultures it increases cAMP concentration leading to inhibition of proliferation....

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Comparative Study 2002; 23(Suppl 1): 61-66 PubMed PMID: 12019354 Citation  Keywords:  Animals, Antioxidants:pharmacology, Humans, Immunity:drug effects, Melatonin:pharmacology, Pineal Gland:physiology, Receptors, Cell Surface:physiology, Receptors, Cytoplasmic and Nuclear:physiology, Receptors, Melatonin, Seasons,.   

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

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Journal Article 2002; 23(Suppl 1): 50-54 PubMed PMID: 12019352 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacology, Antioxidants:pharmacology, Apoptosis:drug effects, Bromodeoxyuridine, Cell Division:drug effects, Colonic Neoplasms:drug therapy, Indoles:pharmacology, Ligands, Melatonin:antagonists & inhibitors, Mice, Mice, I.   

OBJECTIVES: Our previous study suggest that oncostatic action of melatonin (MLT) depends mainly on nuclear RZR/ROR receptors. However, we cannot exclude the involvement of membrane receptors in the control of tumor growth. In the present study the effects of MLT and N-[(4-methoxy-1H-indol-2-yl)methyl]propanamide (UCM 386 - antagonist of membrane MT(1) receptor and partial agonist of membrane MT(2) receptor) on murine transplantable Colon 38 cancer were investigated in vitro and in vivo conditions.

MATERIAL AND METHODS: The experiments were performed on adult male B6D2F1 mice strain. In vitro the cell proliferation was measured using modified Mosmann method. In the experiment performed in vivo, we assessed the cell proliferation, apoptosis and proliferation/apoptosis ratio (P/A). The incorporation of bromodeoxyuridine into tumor cell nuclei was used as an index of cell proliferation (labeling index-LI). The labeling of apoptotic cells according to TUNEL method was considered as an index of apoptosis (AI).

RESULTS: In vitro MLT and UCM 386 decreased the cell proliferation, but administration of MLT and UCM 386 together did not change the inhibitory effect of MLT alone. In vivo MLT and UCM 386 alone decreased LI and the addition of UCM 386 to MLT did not diminish the antiproliferative effect of MLT. Melatonin and UCM 386 injected alone also increased the AI. Moreover, both compounds given together exerted the additive effect on tumor apoptosis. MLT and UCM 386 alone or together also significantly decreased P/A ratio which is additional parameter confirming the inhibition of tumor growth.

CONCLUSION: The obtained data together with our earlier observations suggest that oncostatic effect of MLT depends on acting via both MT(2) and RZR/ROR nuclear receptors...

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Journal Article 2002; 23(Suppl 1): 45-49 PubMed PMID: 12019351 Citation  Keywords:  Antioxidants:pharmacology, Cell Cycle:drug effects, DNA:metabolism, Electrophoresis, Flow Cytometry, Humans, Male, Melatonin:pharmacology, Mutation:genetics, Prostatic Neoplasms:metabolism, Receptors, Androgen:drug effects, Response Elements:drug effects,.   

OBJECTIVES: The pineal hormone melatonin inhibits the growth of benign human prostate epithelial cells and the androgen-dependent prostate cancer LNCaP cells. In the androgen-nonresponsive prostate carcinoma PC3 cells melatonin inhibits cell growth only at high but not low cell density. We have recently found that melatonin causes nuclear exclusion of the AR and attenuates it transcriptional activity in LNCaP cells as well as PC3 cells stably transfected with a wild type AR expressing vector (PC3-AR). The aim of this study was to investigate whether melatonin inhibits effects of AR on cell growth in PC3-AR cells and whether inhibition of AR DNA binding is involved.

METHODS: The effects of androgen, melatonin and their combination on the growth of the PC3-AR cells and on AR DNA binding in PC3-AR and LNCaP cells were studied.

RESULTS: DHT suppressed cell growth in the PC3-AR cells and enhanced AR binding to the androgen responsive element (ARE). Melatonin had no effect on cell growth in the absence of DHT but counteracted the androgen-induced inhibition at low androgen concentrations. Melatonin did not suppress and even slightly enhanced the capacity of AR binding to the ARE in the PC3-AR as well as in LNCaP cells.

CONCLUSIONS: Attenuation by melatonin of AR activity in the prostate cancer cells is not due to suppression of AR binding to the ARE, and is presumably caused by its effects on AR protein interaction and intracellular trafficking....

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Journal Article 2002; 23(Suppl 1): 39-44 PubMed PMID: 12019350 Citation  Keywords:  Animals, Anticarcinogenic Agents:pharmacology, Antioxidants:pharmacology, Carcinogens:antagonists & inhibitors, Humans, Melatonin:pharmacology, Oxidative Stress:physiology,.   

: The complex process of carcinogenesis is, to a large extent, due to oxidative stress. Numerous indicators of oxidative damage are enhanced in the result of the action of carcinogens. Several antioxidants protect, with different efficacy, against oxidative abuse, exerted by carcinogens. Recently, melatonin (N-acetyl-5-methoxytryptamine) and some other indoleamines have gained particular meaning in the defense against oxidative stress and, consequently, carcinogenesis. Some antioxidants, like ascorbic acid, play a bivalent role in the antioxidative defense, revealing, under specific conditions, prooxidative effects. Among known antioxidants, melatonin is particularly frequently applied in experimental models of anticarcinogenic action. In the numerous studies, examining several parameters of oxidative damage and using several in vitro and in vivo models, this indoleamine has been shown to protect DNA and cellular membranes from the oxidative abuse caused by carcinogens. When either preventing or decreasing the oxidative damage to macromolecules, melatonin also protects against the initiation of cancer. The protection provided by melatonin and some other antioxidants against cellular damage, due to carcinogens, make them potential therapeutic supplements in the conditions of increased cancer risk....

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