The pineal gland hormone melatonin (MEL) controls seasonal breeding by regulating feedback and behavioral actions of gonadal steroid hormones. MEL may also shift the phase of endogenous daily (circadian) rhythms, or modulate entraining effects of light. Both circadian rhythms and seasonal reproduction depend upon the suprachiasmatic nucleus of the hypothalamus (SCN). The high affinity, Gi-coupled mel-1a membrane receptor apparently mediates reproductive and at least some of the circadian effects of MEL. The proposed experiments will give us a more complete understanding of the distribution of mel-1a receptor mRNA and the phenotype of cells which express it in hamsters, and will explore the possible physiological implications of these findings. The first specific aim is to determine whether mel-1a receptor mRNA is expressed in VIPergic and light-responsive mel-1a cells in the SCN of Siberian hamsters, whose response to MEL depends upon integrity of the SCN. The second specific aim will evaluate the possible roles of mel-1a, VIPergic and vasopressinergic cells in outputs of the SCN which might contribute to effects of MEL in photoperiodism and circadian entertainment in Siberian hamsters. We will determine whether cells which are retrogradely labeled from projection fields of the SCN contain mel-1a mRNA. We will determine whether photoperiod or pinealectomy influence the pattern of release of AVP or VIP in SCN terminal fields. The third specific aim will evaluate the functional significance of the patterns of colocalization discovered in the experiments. Agonists or antagonists of AVP or VIP will be applied to projection fields of SCN efferents, and intraventricularly, in order to determine the role of these peptides in photoperiodic effects. If we find that mel-1a receptors are expressed in retinally responsive SCN cells, we will determine whether application of physiological concentrations of MEL to the SCN can influence circadian phase or modulate phase-shifting effects of light in vivo. These experiments will clarify the basic function of the circadian pacemaker and the actions of MEL. This is especially relevant to human health and welfare, since millions of Americans have been self-administering MEL in the belief that it will have a wide range of beneficial effects. Our results will have applications to human pathologies including jet lag, sleep disorders, seasonal depression, and infertility.
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