The overall objective of this proposal is to investigate the hypothalamic control of gonadotrophin release in the female rhesus monkey. The goal of this proposal are to characterize the nature of the LHRH pulse generating system and to investigate the manner in which the LHRH pulse generating system is controlled by ovarian steroid hormones, by neurotransmitters and by the interaction of both. Since during the previous funding period we have established a reliable method for measurements of LHRH and catecholamine neurotransmitters in perfusates obtain from the stalk-median eminence of unanesthetized monkeys, we will attempt to accomplish the goals with in vivo experiments. In the first series of experiments the question of whether catecholamine neurons are critically involved in the LHRH pulse generating mechanism will be addressed in ovariectomized monkeys. This is a logical extension of our recent finding that LHRH and norepinephrine (NE) pulses from the stalk-median eminence are synchronous. Catecholamine neurotransmissions to the LHRH neurosecretory system will be blocked by catecholamine receptor antagonists as well as catecholamine synthesis blockers, and changes in LHRH pulsatility and the release of catecholamines and their metabolites will be determined by push-pull perfusion methods. The roles of NE, dopamine (DA) and ephinephrine (E) in the control of LHRH pulses will be examined individually or in combination. In order to further characterize the LHRH pulse generator, single unit activity of the medial basal hypothalamic neurons will be correlated with simultaneous measurement of LHRH and NE release. In the second series of experiments the question of whether the positive feedback action of progesterone of LHRH and LH release requires alpha-adrenergic and/or DA mechanisms will be examined in ovariectomized, estrogen-primed animals. Agonists and antagonists of catecholamines and E synthesis blockers will be administered systemically or into the stalk-median eminence through a push-pull cannula, changes in pulsatile LHRH release will be determined. Release of catecholamines and their metabolites and concomitant release of LHRH will also be determined: In the third series of experiments negative and positive feedback effects of estrogen of LHRH and catecholamine release will be examined in ovariectomized monkeys. It is our hope to obtain a clear picture of the LHRH pulse generating system. Results from the project will provide further insight into the mechanisms by which the hypothalamus controls the release of gonadotropin in primates.
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