The proposed research is designed to test further the hypothesis that modulation of the gonadotropin receptor-adenylyl cyclase system is an important mechanism regulating corpus luteum function in primates during the menstrual cycle and early pregnancy. Based on progress in this laboratory, specific aims are presented: (a) to determine whether bona-fide receptors for luteinizing hormone (LH) and chorionic gonadotropin (CG) are masked in luteal membranes and to identify conditions which mask/unmask receptors, (b) to correlate the number of available, occupied, and masked LH-CG receptors with the functional state of the corpus luteum during the menstrual cycle, (c) to investigate in vitro the direct effects of potential luteolytic agents on the gonadotropin receptor-adenylyl cyclase system, (d) to compare the effect of in vivo exposure to hCG (designed to mimic early pregnancy levels) on gonadotropin receptor-adenylyl cyclase activity in young vs. mature corpora lutea, and (e) to develop an in vivo model examining the ability of intraovarian estrogen and prostaglandin to modulate gonadotropin receptor-adenylyl cyclase activity and the function of the primate corpus luteum. The adult, female rhesus monkey continues as the animal choice for our studies on the primate corpus luteum, with comparative studies employing luteal tissue from the pseudopregnant rat and the pig. Available and masked receptors will be characterized via specific 125I-labeled hLH/hCG binding to macaque luteal preparations before and after exposure to unmasking agents (e.g., ethanol). Adenylyl cyclase activity will be assessed from the conversion of [Alpha32P] ATP to [Alpha32P] cyclic AMP by luteal preparations. These studies will provide new information on the cellular mechanims regulating the corpus luteum during the menstrual cycle and early pregnancy, with application to the control of human fertility and infertility. In particular, the investigation will determine whether heterologous and homologous regulation of the gonadotropin receptor-adenylyl cyclase system, by potent luteolytic agents and gonadotropins, respectively, plays an important role in the regulation of the function/lifespan of the primate corpus luteum.
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