The lutropin/choriogonadotropin receptor (LHR), present on the cell surface of certain cells in the ovaries and testes, plays a critical role in reproductive physiology. Recent studies from our lab and others on the cloning of the cDNA for this receptor have shown that it is a member of the family of G protein-coupled receptors and thus contains the characteristic feature of seven membrane-spanning domains oriented with the C-terminus on the cytoplasmic face. Unlike many other G protein- coupled receptors, however, the LHR contains a large extracellular domain which we and others have shown to be sufficient for high affinity binding of hCG. The focus of the present grant is to continue some studies that have already begun and to initiate others that will yield information about the structure and function relationships of the LHR and in turn on the mechanism of action of the receptor. Specifically, the aims of the grant are to: A. Determine the sites of N-linked glycosylation on the rLHR and their role, if any, on signal transduction B. Continue studies on identifying regions of the rLHR which mediate hormone-occupied receptor internalization C. Identify regions of the rLHR involved in activating G proteins D. Investigate the mechanisms of rLHR activation The information learned from these studies will contribute to our understanding of G protein-coupled receptors in general (which are integral to various physiological systems) and more specifically will further our understanding of the role of this receptor in reproductive physiology. As such, it is anticipated that the results of these studies will aid us in the future in understanding, diagnosing, and treating certain forms of infertility, as well as in the design of novel contraceptive agents to suppress fertility.
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