Abstract
The mechanism(s) by which melatonin (MEL) can regulate gonadotropin secretion remains unresolved. Accordingly, we used acute in vitro incubations of male rat hypothalamic tissues to investigate effects of MEL on hypothalamic gonadotropin-releasing hormone (GnRH) secretion. At 10:00h (3.5 after lights on), addition of 1 nM MEL to the medium inhibited (p=0.028) GnRH release from the median eminence (ME) by 24%, 100 nM MEL had no significant effect on GnRH release, and 10 µM MEL tended to inhibit (p=0.056, 21%) GnRH release. At 15:00 h, none of these MEL dosages significantly altered GnRH release from the ME. When the effect of a lower range of MEL dosages was evaluated, 1 nM MEL again inhibited (24%, p=0.032) GnRH release from the ME at 10:00 h, and a linear dose-response relationship between initially increasing dosages (0, 0.01, 0.1, 1 nM) of MEL treatment and decreasing GnRH release was evident (r=−0.88), although a further 10 fold increase in MEL dosage (10 nM) resulted in a loss of suppression by MEL. Treatment with these dosages of MEL did not significantly alter ME GnRH release at 15:00 h. In contrast to the results with the ME alone, treatment with 0.1 µM MEL increased (p=0.018) GnRH release from the arcuate-median eminence region (ARC-ME) by 60.2% at 10:00 h, whereas treatment with either 0.001 or 10 µM MEL did hot significantly affect GnRH release. Treatment with these dosages of MEL did not significantly alter ARC-ME GnRH release at 15:00 h. These results suggest that there are clearly diurnal mechanisms within the male rat hypothalamus by which MEL can either facilitate or suppress GnRH release.
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References
Tamarkin L, Baird C.J., Almeida O.F.X., Melatonin: a coordinating signal for mammalian reproduction? Science 227: 714, 1985.
Reiter R.J., Neuroendocrinology of melatonin. In: Miles A., Philbrick D.R.S., Thompson C. (Eds.), Melatonin. Clinical Perspectives. Oxford University Press, Oxford, 1988, p. 1.
Kinson G.A., Robinson S. Gonadal function of immature male rats subjected to light restriction, melatonin administration and removal of the pineal gland. J. Endocrinol. 47: 391, 1970.
Kinson G.A., Peat F., The influences of illumination, melatonin, and pinealectomy on testicular functions in the rat. LifeSci. 10: 259, 1971.
Ramaley J.A., Bunn E.L., Seasonal variations in the onset of puberty in rats. Endocrinolog 91: 611, 1972.
Lang U., Aubert M.L., Rivest R.W., Vinas-Bradtke J.C., Sizonenko P.C. Daily afternoon administration of melatonin does not irreversibly inhibit sexual maturation in the male rat. Endocrinolog 115: 2303, 1984.
Rivest R.W., Lang U., Aubert M.L, Sizonenko P.C., Daily administration of melatonin delays rat vaginal opening and disrupts the first estrous cycles: evidence that these effects are synchronized by the onset of light. Endocrinolog 116: 779, 1985.
Hoffman J.C., Effect of photoperiod on estrous cycle length in the rat. Endocrinolog 83: 1355, 1968.
Reiter R.J., Sorrentino S., Inhibition of luteinizing hormone release and ovulation in PMS-treated rat by peripherally administered melatonin. Contraception 4: 385, 1971.
Blask M.S., Mann D.R., Antigonadotrophic and prolactin inhibitory effects of melatonin in anosmic rats. Neuroendocrinolog 29: 406, 1979.
Blask D.E., Nodelman J.L., Leadem C.A., Richardson B.A. Influence of exogenously administered melatonin on the reproductive system and prolactin levels in underfed male rats. Biol. Reprod. 22: 507, 1980.
Reiter R.J., Petterborg L.J., Trakulrungsi C, Traku-Irungsi W.K., Surgical removal of the olfactory bulbs increases sensitivity of the reproductive system of female rats to the inhibitory effects of late afternoon melatonin injections. J. Exp. Zool. 212: 47, 1980.
Zisapel N., Egozi Y., Laudon M., Circadian variations in the inhibition of dopamine release from adult and newborn rat hypothalamus by melatonin. Neuroendocrinolog 40: 102, 1985.
Rasmussen D.D., The interaction between mediobasohypothalamic dopaminergic and endorphinergic neuronal systems as a key regulator of reproduction: an hypothesis. J. Endocrinol. Invest. 14: 323, 1991.
Rasmussen D.D., Dopamine-opioid interaction in the regulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Neuroendocrinol. Lett. 13: 419, 1991.
Gambacciani M., Yen S.S.C., Rasmussen D.D., GnRH release from the mediobasal hypothalamus: in vitro regulation by oxytocin. Neuroendocrinolog 42: 181, 1986.
Gambacciani M., Yen S.S.C., Rasmussen D.D., GnRH release from the mediobasal hypothalamus: in vitro inhibition by corticotropin-releasing factor. Neuroendocrinolog 43: 533, 1986.
Rasmussen D.D., Kennedy B.P., Ziegler M.G., Nett T.M., Endogenous opioid inhibition and facilitation of gonadotropin-releasing hormone release from the median eminence in vitro: potential role of catecholamines. Endocrinolog 123: 2916, 1988.
Vanecek J., Pavlik A., Illnerov H., Hypothalamic melatonin-receptor sites revealed by autoradiography. Brain Res. 435: 359, 1987.
Weaver D.R., Rivkees S.A., Reppert S.M., Autoradiographic localization of iodomelatonin binding sites in hypothalamus of three rodent species. Endo. Soc. Abstr. 70: 265, 1988 (Abstract).
Wilkinson L. SYSTAT: The System for Statistics. SYSTAT, Inc., Evanston, IL, 1988, p. 484.
Rotsztejn W.H., Charli J.L, Pattou E., Kordon C., Stimulation by dopamine of luteinizing hormone-releasing hormone (LHRH) release from the mediobasal hypothalamus in male rats. Endocrinolog 101: 1475, 1977.
Nakazawa K., Marubayashi U., McCann S.M., Mediation of the short-loop negative feedback of luteinizing hormone (LH) on LH-releasing hormone release by melatonin-induced inhibition of LH release from the pars tuberalis. Proc. Natl. Acad. Sci. USA 88: 7576, 1991.
Bugnon C, Bloch B., Lenys D., Gouget A., Fellmann D. Comparative study of the neuronal populations containing beta-endorphin, corticotropin and dopamine in the arcuate nucleus of the rat hypothalamus. Neurosci. Lett. 74: 43, 1979.
Giovarelli M., Santoni A., Jemma C, Musso T., Giuf-frida A.M., Cavallo G., Landolfo S., Forni G. Obligatory role of IFN-gamma in induction of lym-phokine-activated and T lymphocyte killer activity, but not in boosting of natural cytotoxicity. J. Immunol. 141: 2831, 1988.
Negro-Vilar A., Ojeda S.R., McCann S.M., Catecholaminergic modulation of luteinizing hormone-releasing hormone release by median eminence terminals in vitro. Endocrinolog 104: 1749, 1979.
Richardson S.B., Prasad J.A., Hollander C.S. Acetylcholine, melatonin, and potassium depolarization stimulate release of luteinizing hormone-releasing hormone from rat hypothalamus in vitro. Proc. Natl. Acad. Sci. USA 79: 2686, 1982.
Cagnacci A., Elliot J.A., Yen S.S.C., Amplification of pulsatile LH secretion by exogenous melatonin in women. J. Clin. Endocrinol. Metab. 73: 210, 1991.
Aleen F.A., Weitzman E.D., Weinberg U., Suppression of basal luteinizing hormone concentrations by melatonin in postmenopausal women. Fertil. Steril. 49: 923, 1985.
Reid R.L., Quigley M.E., Yen S.S.C., The disappearance of opioidergic regulation of gonadotropin secretion in postmenopausal women. J. Clin. Endocrinol. Metab. 57: 1107, 1983.
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Rasmussen, D.D. Diurnal modulation of rat hypothalamic gonadotropin-releasing hormone release by melatonin in vitro . J Endocrinol Invest 16, 1–7 (1993). https://doi.org/10.1007/BF03345819
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DOI: https://doi.org/10.1007/BF03345819