Pineal melatonin is an endogenous regulator of reproduction, metabolism, and circadian timekeeping in juvenile and adult mammals. It acts as a neuroendocrine transducer since its daily pattern of secretion is regulated by light, particularly by daylength or photoperiod. This hormone travels through the circulation to receptors on target organs whose location has not been clearly established. Recently, techniques have become available for identifying melatonin receptor binding sites in the central nervous system by using the radioligand 2-[125I]-iodomelatonin (IMEL). Activation of these sites by melatonin appears to modulate neurotransmitter release, receptor number and hormone secretion. To further study the function of IMEL binding sites, this project will use the annual reproductive cycle in the Djungarian hamster as a model system.
The specific aims for this project are: 1) biochemical and pharmacological characterization of IMEL binding sites in the hypothalamus, 2) investigation of the regulation of these sites by time of day and melatonin, 3) localization and quantitation of IMEL binding sites in discrete brain regions at various phases of the annual cycle, and 4) investigation of the functional significance of the IMEL binding sites in the annual reproductive cycle. The studies pertaining to specific aims 1 and 2 will use radioligand binding techniques to identify IMEL binding sites and examine their physiological regulation. The experiments related to specific aim 3 will use quantitative autoradiography to measure IMEL binding sites in discrete brain regions after various photoperiodic treatments. The studies proposed under specific aim 4 will use regions labelled with IMEL in mediating photoperiodic information. Other studies will investigate the effect of melatonin on serotonergic turn-over rate in terminal fields labelled with IMEL. Immunocytochemical studies will characterize selected cell populations and afferent inputs in regions labelled with IMEL. These studies will provide an important model system for studying environmental and hormonal effects on neuroendocrine function, which is my longterm research goal. The results of these studies will help to elucidate the sites and mechanisms of action of melatonin in regulating reproduction and other physiological functions. Although the results will be obtained from studies of laboratory animals, they are of importance for human health since melatonin is being used clinically to alleviate sleep and mood disorders.
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