The goal of the present studies is to determine the sequence of events involved in luteinizing hormone (LH) receptor synthesis, and regulation of these events by physiological agents that have been shown to alter the expression of LH receptor binding on gonadal tissue. Thus, the specific aims of the grant are 1) to prepare and 2) characterize monoclonal antibodies against the receptor as specific reagents for following the synthesis of the glycoprotein LH receptor in cultured cells that have been metabolically labeled using radiolabeled amino acids or sugars, 3) outline the translational and post-translational modifications of the LH receptor that occur prior to and following insertion into the surface membrane and expression of receptor functions, i.e. the binding of hormone and activation of adenylate cyclase and 4) evaluate changes in the sequelae determined in #3 that occur when receptor density is increased by estradiol or platelet-derived growth factor (PDGF) or attenuated by epidermal growth factor (EGF) or human chorionic gonadotropin (hCG). The LH-receptor plays an initial and crucial role in mediating LH-induced physiological effects in gonadal tissue. Consequently, these studies should outline the molecular basis for LH receptor expression in a target cell, and provide new insights into the biochemical events that result in a functional receptor molecule as well as changes in these events that are elicited by modulators of LH receptor density and function, e.g. estradiol, EGF, PGDF and the agonist hCG itself.
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