Hormonal regulation of steroidogenic enzyme expression in granulosa cells during the peri-ovulatory interval in monkeys

Although progesterone plays an essential role in ovulation and the luteiniz iation of the primate follicle, the expression of cellular components requi red for progesterone synthesis and their control is not well defined. This study was designed to determine the time course and gonadotrophin versus st eroid regulation of the transcription of genes involved in progesterone syn thesis in peri-ovulatory follicles. Granulosa cells or whole ovaries were o btained from macaques undergoing controlled ovarian stimulation either befo re (0 h) or up to 36 h following the administration of an ovulatory human c horionic gonadotrophin (HCG) bolus with or without a 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) inhibitor, with or without a non-metabolizable p rogestin. Granulosa cell concentrations of low density lipoprotein receptor (LDL-R) and steroidogenic acute regulatory protein (StAR) mRNA increased t ransiently 12 h following HCG administration (P < 0.05) at which time stero id depletion tended to reduce StAR mRNA (P = 0.06). At 36 h post-HCG proges terone suppressed the LDL-R mRNA levels (P < 0.05). P450 side-chain cleavag e (P450scc) mRNA decreased in a time-dependent fashion up to 24 h, whereas 3 beta-HSD mRNA increased within 12 h of HCG administration (P < 0.05) in a steroid-independent manner. Whole ovarian 17 alpha-hydroxylase (P450c17) a nd granulosa cell P450 aromatase (P450arom) mRNA declined in a time-depende nt fashion; by 36 h after HCG administration, steroid depletion increased P 450arom mRNA, although progestin replacement did not return aromatase to co ntrol values (P < 0.05). These data demonstrate diverse patterns of steroid ogenic enzyme expression that generally reflect the conversion of the macaq ue peri-ovulatory follicle from an oestrogen to progesterone producing glan d. Although mRNAs associated with progesterone synthesis and metabolism are primarily regulated by gonadotrophins, cholesterol uptake and utilization may be modulated locally by steroids in luteinizing granulosa cells.