Progesterone receptors (PR) are expressed by granulosa cells (CG) in the maturing follicle after, but not before, the ovulatory gonadotropin surge in natural [i.e., midcycle surge of luteinizing hormone (LH) and follicle stimulating hormone (FSH)] or artificial [i.e., a midcycle bolus of human chorionic gonadotropin (hCG)] menstrual cycles. This project was designed to determine whether gonadotropins act directly or indirectly via prostaglandins (PG) or progesterone (P) to induce PR expression in nonluteinized CG's. Granulosa cells isolated from gonadotropin-treated rhesus monkeys not receiving an ovulatory stimulus were cultured (8 x 104 cells/well) on fibronectin coated 8-well glass chamber slides in chemically-defined medium containing human low-density lipoprotein (25 fg hLDL/ml) (control) with or without LH (10 or 400 ng/ml), hCG or FSH (400 ng/ml), PGE2, PGF2` or PGA2 (14 fM), trilostane (TRL), a 3 -hydroxy-steroid dehydrogenase inhibitor (250 ng/ml) or flurbiprofin (FLUR), a prostaglandin synthase inhibitor (100 fM). Spent medium was collected daily for 2 days and saved for progesterone determination by RIA. On days 0 and 2, cells were frozen in liquid propane and PR determined by immunocytochemistry. Progesterone production and PR expression was significantly increased (P<0.05) over control values in cultures containing 10 or 400 ng/ml LH and 400 ng/ml FSH or hCG. Trilostane significantly (P<0.05) inhibited P production and tended to decrease the percent of PR-positive cells. Exposure to LH (400 ng/ml) overcame both P production and PR expression inhibition by TRL. PGE2 significantly increased (P<0.05) P production, but none of the PG altered PR expression compared to control values. FLUR had no effect on P production but significantly (P<0.05) decreased the percent PR-positive cells compared to controls. PGE2, as well as LH, prevented the decrease caused by FLUR. Thus, exogenous gonadotropins, but not PG, stimulated PR expression in nonluteinized monkey granulosa cells during culture. However, locally produced PG's may also facilitate PR expression.
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