Since progesterone (P) receptors are present in luteal cells of rhesus monkeys, we are testing the hypothesis that actions attributed to luteinizing hormone (LH) and chorionic gonadotropin (CG) are mediated, at least in part, by P produced in response to these gonadotropins. Studies currently focus on whether P mediates LH actions leading to rupture and luteinization of the follicle. Experiments were designed (1) to elucidate the dynamics of cellular and molecular events during the Aperiovulatory interval,@ and (2) to determine if inhibition of steroid synthesis and/or progestin replacement alters these events in the presence of an ovulatory gonadotropin stimulus. Female rhesus monkeys received gonadotropins to promote the development of multiple preovulatory follicles. Then animals received an ovulatory gonadotropin (hCG) bolus alone or with the steroid synthesis inhibitor Trilostane, with and without progestin replacement. Granulosa cells were collected before (0 hr), or 12, 14 and 36 hr after administering the hCG bolus. First, the hCG bolus rapidly (? 12 hr) stimulated increases in mRNAs encoding the P receptor (PR) and androgen receptor (AR), whereas mRNAs for estrogen receptor (ER) ? and ? did not change or decreased, respectively, within 36 hr. Steroid ablation prevented the rise in PR mRNA and reduced ER? mRNA; these effects were reversed by progestin replacement. Second, levels of mRNAs encoding interstitial collagenase (matrix metalloproteinase-1, MMP-1), gelatinase-A (MMP-2), matrilysin (MMP-7), as well as their endogenous tissue inhibitors (TIMP-1 and -2), increased within 12 hr, whereas gelatinase B (MMP-9) increased by 36 hr post-hCG. Steroid ablation decreased mRNA levels for MMP-1, -7, and -9, as well as TIMP-1 and -2, and progestin replacement restored MMP-1 and TIMP-1 mRNA levels. Thus, (1) there may be diverse roles for progesterone, as well as androgens and estrogens, via receptor-mediated pathways, throughout the periovulatory interval, and (2) one of the primary actions of progesterone, and possibly other steroids, may be to promote the expression of specific collagenolytic proteases and their inhibitors. This research should provide novel insight into mechanisms leading to certain types of infertility and suggest unique methods for controlling fertility by preventing ovulation in women. FUNDING NIH HD20869, HD18185 PUBLICATIONS Chaffin CL, Hess DL, Stouffer RL. Dynamics of progesterone (P) and progesterone receptor (PR) expression in the primate follicle during the periovulatory interval. In Endocrine Society Program and Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 184 (abstract #P1-306). Chaffin CL, Stouffer RL. Progesterone (P) promotes the expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the primate periovulatory follicle. In Society for the Study of Reproduction Program and Abstracts 31st Annual Meeting (held in College Station, TX, August 8-11, 1998), p 110 (abstract #126). Duffy DM, Stouffer RL, Chaffin CL. Noncoordinated expression of estrogen receptor ? and ? in the ovulatory follicle and the corpus luteum of the rhesus monkey. In Society for the Study of Reproduction Program and Abstracts 31st Annual Meeting (held in College Station, TX, August 8-11, 1998), p 108 (abstract #118). Chaffin CL, Stouffer RL. Dynamics and steroid regulation of oocyte maturation in macaque follicles during the periovulatory interval. In International Symposium on Ovulation Evolving and Clinical Concepts (held in Salt Lake City, UT, September 24-27, 1998), p 33 (abstract #1).
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