Recent data from this laboratory suggest that the primate corpus luteum (CL) contains progesterone (P) and androgen (A) [but not estrogen (E)] receptors (R) and that the ovulatory gonadotropin surge induces PR in luteinizing granulosa cells. The proposed experiments are designed: (a) to investigate steroid R gene activity in the primate ovary and whether the midcycle gonadotropin surge increases PR mRNA levels in the developing corpus luteum, (b) to examine the role of gonadotropins (LH and CG) in the maintenance and """"""""rescue"""""""" of PR (but not AR or ER) in the CL of the menstrual cycle and early pregnancy, respectively, (c) to determine whether LH and CG act directly or indirectly [via prostaglandins (PGs) or steroids] to induce or maintain PR and its mRNA in luteal cells, and (d) to consider the role of progesterone/PR- and androgen/AR-mediated events in the development, function and regression of the primate corpus luteum during the menstrual cycle. Cells from pre- and post-ovulatory follicles and corpora lutea will be collected from rhesus monkeys at specific stages in spontaneous and artificial (gonadotropin-treated) menstrual cycles. GnRH antagonist and PG or steroid synthesis inhibitors (or vehicle) will be administered prior to tissue collection. Steroid Rs will be examined by immunocytochemistry, radioligand binding assays and Western blot analyses. Steroid R mRNAs will be detected by reverse transcription-polymerase chain reaction and PCR-amplified cDNA sequenced. Steroid R mRNAs will be quantitated by the ribonuclease protection assay. Cells will be cultured in the presence and absence of gonadotropins (FSH, LH, CG), PGs (e.g., PGE2 and F2alpha), steroids (P, A, E) or PG and steroid inhibitors to determine if LH/CG or gonadotropin-stimulated cell products directly regulate PR or mRNA expression. In vivo and cell culture approaches will determine if P and A act locally to modulate the development (including periovulatory events) and function (basal and LH/CG-sensitive PG and peptide synthesis) by the macaque corpus luteum. These studies should establish whether the primate corpus luteum of the menstrual cycle and early pregnancy contains classical steroid Rs and will likely identify a new action for luteotropic gonadotropins--the regulation of PR and hence P action. The first detailed investigation on the roles of P and A in the primate CL will be performed. This work should provide unique insight into gonadotropin-dependent, steroid-regulated processes that locally modulate primate luteal function, with direct applications to controlling fertility and infertility in women.
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