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Inverse Relationship Between the Expression of Messenger Ribonucleic Acid for Peroxisome Proliferator-Activated Receptor and P450 Side Chain Cleavage in the Rat Ovary¹

Department of Animal Science,² Iowa State University, Ames, Iowa 50011-3150 Department of Obstetrics and Gynecology,³ University of Kentucky, Lexington, Kentucky 40536-0298

Messenger RNA for peroxisome proliferator-activated receptor (PPAR) has been found in granulosa cells, and its expression decreases after the LH surge. We determined which developmental stage of ovarian follicle expresses mRNA for PPAR and evaluated the impact of PPAR agonists on steroidogenesis. Ovaries were collected from immature eCG/hCG-treated rats at 0 (no eCG), 24, and 48 h post-eCG and 4 and 24 h post-hCG. Ovarian tissue was serially sectioned and processed for in situ hybridization to localize mRNA corresponding to PPAR, aromatase, and the LH receptor, and P450 side chain cleavage (P450_SCC) and to determine whether apoptotic cells were present. During follicular development, there was no correlation between the expression of mRNAs for PPAR and aromatase or the presence of apoptotic cells, but a general inverse correlation was observed between the expression of PPAR mRNA and LH receptor mRNA. At 4 h post-hCG, follicles expressing P450_SCC mRNA had lost expression of PPAR mRNA. This inverse pattern of expression between PPAR and P450_SCC mRNAs was also observed 24 h post-hCG, with developing luteal tissue expressing high levels of P450_SCC mRNA but little or no PPAR mRNA. To determine the impact of PPAR on steroidogenesis, granulosa cells were collected from ovaries 24 h post-eCG and cultured alone, with FSH alone, or with FSH in combination with the PPAR agonists ciglitazone or 15-deoxy-^12,14-prostaglandin J₂ (PGJ₂). Treatment of granulosa cells with PGJ₂ stimulated basal progesterone secretion, whereas ciglitazone or PGJ₂ had no significant effect on FSH-stimulated steroid production. These findings suggest that 1) PPAR may regulate genes involved with follicular differentiation and 2) the decline in PPAR in response to LH is important for ovulation and/or luteinization.

¹ This work was supported by grants NIH P20 RR 15592 (to T.E.C. and C.M.K.) and NIH HD40842 (to C.M.K.).

² Correspondence: Carolyn M. Komar, Department of Animal Science, Iowa State University, 2356 Kildee Hall, Ames, IA 50011-3150. FAX: 515 294 4471; ckomar{at}iastate.edu

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