The present project is divided into three areas of focus. The first area provides information on the structure of the GnRH receptor and early actions following the interaction of the receptor with GnRH and its analogs. These studies should advance our understanding of the receptor in the mechanism of GnRH action. The second area provides information on the relationship between the multiple effector mechanisms already implicated in GnRH action with the multiple actions stimulated by the releasing hormone (release of multiple endocrine substances, regulation of target cell responsiveness, biosynthesis, and regulation of receptor number). This is important since considerable confusion remains regarding these relationships. The third area involves understanding the molecular sites of action of activin and inhibin in relation to GnRH action and are significant to understand the actions of these agents in vivo. Studies dealing with the biochemical and molecular mechanism of gonadotropin releasing hormone (GnRH) action have served to (a) identify new clinical and veterinary uses for GnRH and its analogs, (b) bring these uses to fruition through a rational process based on understanding of the mechanism of hormone action, and (c) provide the means for anticipating, understanding, and ameliorating side-effects of the agents. FDA approvals of GnRH agonists for the treatment of prostate cancer, endometriosis, and precocious puberty, as well as for the use of natural sequence GnRH to induce ovulation, and to test the hypothalamic-pituitary-gonadal axis, are examples of the clinical usefulness derived from these fundamental observations.
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