REGULATION OF LH RECEPTORS AND PROGESTERONE SECRETION

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Progesterone secretion by the corpus luteum is essential for normal pregnancy. Thus, methods to interrupt secretion of this hormone have potential contraceptive applications. In addition, biological anomolies in this system cause infertility in some couples. The first step in stimulation of progesterone secretion by luteinizing hormone (LH) is the interaction of the hormone with its receptor. Therefore, experiments are proposed to characterize further this interaction. First, differences in the biological response of luteal cells to human chorionic gonadotropin (hCG) and luteinizing hormone (LH), which interact with the same receptor, will be studied. The effects of pulses of the two hormones on progesterone secretion by slices of luteal tissue in a perifusion system will be examined to determine if hCG induces a prolonged steroidogenic response, as seen in other tissues. Since it is known that hCG-LH receptor complexes remain on the surface of luteal cells 50 times longer than LH-LH receptor complexes we will also compare the lateral mobility of hCG-LH receptor complexes and LH-LH receptor complexes in luteal cell membranes using a laser photobleach recovery technique. Second, recent identification and characterization of two types of steroidogenic luteal cells lead to experiments designed to: 1) identify the luteal cell types which originate from follicular granulosal and thecal cells; 2) characterize the cell type(s) which bind LH, and PGF(2 alpha) in vivo; and 3) define the nature of the cell-to-cell interactions which results in luteal regression during the reproductive cycle or maintenance of the corpus luteum during pregnancy. In vivo and in vitro procedures will be used in these studies. Third, since secretion of progesterone by the corpus luteum appears to be more dependent upon the number of receptors present for LH than on the levels of this hormone in blood, the mechanisms involved in loss and renewal of receptors for LH will be studied using monoclonal antibodies against the LH receptor and/or methods which allow LH or hCG to be covalently linked to the receptor. Finally, the role of the GTP-binding protein in hormonal activation of adenylate cyclase will be studied using photoaffinity analogs of GTP. The results of these studies will provide new information regarding the complex biological mechanisms which regulate progesterone secretion from the corpus luteum.