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Journal Article 2002; 23(Suppl 1): 88-91 PubMed PMID: 12019359 Citation  Keywords:  Adult, Blood Pressure:drug effects, Circadian Rhythm:physiology, Clinical Trials as Topic, Electromagnetic Fields:adverse effects, Heart Rate:drug effects, Humans, Male, Melatonin:analogs & derivatives, Telephone,.   

OBJECTIVES: It is quite likely that non-visible electromagnetic fields (EMF) may affect melatonin production. Some studies confirmed this hypothesis and showed that extremely low EMF altered pineal function in animals and humans. Thus, it is reasonable to suppose that EMF emitted by cellular phones may also influence secretion of melatonin. The present study sought to evaluate possible effect of the exposure to EMF emitted by cellular phone on 6-hydroxymelatonin sulfate (6-OHMS) excretion, which reflects melatonin levels in blood.

MATERIAL AND METHODS: The examined group consisted of 9 healthy males aged 19-29 years. The experiment was performed under controlled conditions (the light intensity-50 lx till midnight and 0 lx during night). Each person was examined twice: on a day without exposure (control day, C-day) and on a day with continuous exposure (60 min. exposure from cellular phone, frequency 900 MHz, pulsed with 217 Hz, pulse with 576 micros, SAR 1.23 W/kg, E-day). From 7 p.m. to 8 p.m. they used a cellular phone. The subjects did not know which day was E-day, and which was C-day. From 8 p.m. till midnight the subjects listened to music and than they slept till 7 a.m. next day. Urine samples were collected at 7 p.m., at midnight, and at 7 a.m. in the same way in C-day as in E-day. Sample were frozen for later ELISA analysis of 6-OHMS. The 6-OHMS ELISA kit from Immuno-Biological Laboratories (Hamburg) was used for measurement of 6-OHMS. The data were analysed using Wilcoxon matched-pairs signed-ranks test for each subject and for the whole group. We compared 6-OHMS level on the E-day and on the C-day separately for 3 time-points - 7 p.m., midnight, 7 a.m.

RESULTS: Mean 6-OHMS level in both experiments did not differ significantly for any of the respective time points. Circadian variations of 6-OHMS level were detected in all subjects.

CONCLUSIONS: The results of our investigation has demonstrated that EMF emitted by cellular phones has no distinct influence on the melatonin level....

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Journal Article 2002; 23(Suppl 1): 84-87 PubMed PMID: 12019358 Citation  Keywords:  Animals, Anticarcinogenic Agents:pharmacology, Electromagnetic Fields:adverse effects, Humans, Melatonin:pharmacology, Neoplasms:epidemiology,.   

: There is public health concern raised by epidemiological studies indicating that extremely low frequency electric and magnetic fields generated by electric power distribution systems in the environment may be hazardous. Possible carcinogenic effects of magnetic field in combination with suggested oncostatic action of melatonin lead to the hypothesis that the primary effects of electric and magnetic fields exposure is a reduction of melatonin synthesis which, in turn, may promote cancer growth. In this review the data on the influence of magnetic fields on melatonin synthesis, both in the animals and humans, are briefly presented and discussed....

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Journal Article 2002; 23(Suppl 1): 79-83 PubMed PMID: 12019357 Citation  Keywords:  Animals, Cardiovascular Physiological Phenomena, Hemodynamics:physiology, Humans, Melatonin:physiology,.   

: Melatonin concentrations in serum, as well as urinary levels of its main metabolite, 6-sulphatoxymelatonin, decrease with age. In the course of aging, the frequency of heart diseases, both acute and chronic, systematically increases. The evidence from the last 10 years suggests that melatonin influences the cardiovascular system. The presence of vascular melatoninergic receptors/binding sites has been demonstrated; these receptors are functionally linked with vasoconstrictor or vasodilatory effects of melatonin. Melatonin can contribute in cardioprotection of the rat heart, following myocardial ischemia. It has been shown that patients with coronary heart disease have a low melatonin production rate, especially those with higher risk of cardiac infarction and/or sudden death. There are clinical data reporting some alterations of melatonin in human stroke and coronary heart disease. The suprachiasmatic nucleus and, possibly, the melatoninergic system may also modulate cardiovascular rhythmicity. Hypercholesterolemia and hypertension are the other age-related symptoms. People with high levels of LDL-cholesterol have low levels of melatonin. It has been shown that melatonin suppresses the formation of cholesterol by 38% and reduces LDL accumulation by 42%. A 10-20% reduction of cholesterol concentration in women using the B-oval pill has been observed. It is a very important because, even a 10-15% reduction in blood cholesterol concentration has bee shown to result in a 20 to 30% decrease in the risk of coronary heart disease. People with hypertension have lower melatonin levels than those with normal blood pressure. The administration of the hormone in question declines blood pressure to normal range. It has been observed that melatonin, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects. Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of catecholamines, or 4) by relaxing the smooth muscle in the aorta wall....

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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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