Regulation of rat granulosa cell α-inhibin expression by luteinizing hormone, estradiol, and progesterone

OBJECTIVE: Our purpose was to assess the effects of follicle-stimulating hormone, luteinizing hormone, forskolin (an adenylyl cyclase activator), estradiol, and progesterone on α-inhibin promoter activity in an in vitro fusion gene-transfection system. STUDY DESIGN: A fusion gene consisting of the α-inhibin 5' flanking and promoter regions linked to the chloramphenicol acetyl transferase reporter gene was constructed. A granulosa cell line originally derived from an inbred strain of Berlin Duckrey rats was transiently transfected with the fusion gene. Fusion gene activity was determined by measuring chloramphenicol acetyl transferase activity in transfected cells. RESULTS: Both follicle-stimulating hormone and luteinizing hormone activated the α-inhibin promoter. Activity in response to combined luteinizing hormone-forskolin treatment was greater than the summation of the activities of the two treatments individually, suggesting that the effects of luteinizing hormone might be partially mediated by second messengers other than cyclic adenosine monophosphate. Gonadotropin-stimulated activity was diminished by estradiol and combined estradiol-progesterone treatments. CONCLUSIONS: The stimulatory effects of follicle-stimulating hormone and luteinizing hormone on α-inhibin production are mediated at least in part by stimulation of the α-inhibin promoter. The stimulatory effects are blunted by estradiol and estradiol progesterone. These observations may partially explain how α-inhibin is down-regulated in vivo in response to the preovulatory luteinizing hormone surge.