The proposed studies are intended to delineate the role of GnRH in the secretion of pituitary gonadotropins and the modulating effects of gonadal steroids. The mechanisms of GnRH action on the pituitary gland will be investigated. At the pituitary level GnRH can stimulate or inhibit gonadotropin secretion depending upon the manner of GnRH administration. The mechanisms of these paradoxical effects will be studied by measurement of plasma membrane GnRH receptors, mRNA concentrations for the gonadotropin subunits and LH and FSH secretion in different physiological and experimental circumstances. Additionally, as the nature of the intracellular transmission of the GnRH stimulus is unknown, the possibility that GnRH may act directly on the nucleus of the gonadotroph cell via a specific receptor will be determined. These studies will define the relative importance of plasma membrane and nuclear events in the control of gonadotropin synthesis and secretion and will allow insights into the intracellular site of steroid hormone feedback. The paradoxical effects of GnRH have led to clinical applications for both the induction of fertility and for contraception. Knowledge of the mechanisms of these actions is critical in order to provide the basis for rational future therapeutic uses of GnRH and its analogs.
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