Modulation of FSH-controlled steroidogenesis in rat granulosa cells: direct in-vitro effects of LHRH and ICI-118630.
Direct inhibitory effects of LHRH and an LHRH agonist (ICI-118630) on FSH-controlled steroidogenic processes in ovarian granulosa cells were characterized in vitro. Over a 2-day culture period in the presence of testosterone (10(-7) M), FSH (3-3 000 ng/ml) caused dose-dependent increases in the aromatase activity of granulosa cells isolated from oestrogen-pretreated immature rats. Progestogen biosynthesis was stimulated in a similar manner. The presence of LHRH (10(-9) - 10(-7) M) in the culture medium inhibited these responses by right-shifting the dose-response curves. Thus the net effect was one of reduced sensitivity to FSH. ICI-118630 was approximately 10 times more effective than LHRH as an inhibitor of aromatase induction and progestogen biosynthesis in response to FSH. Over a 1-h incubation at concentrations up to 10(-7) M, neither decapeptide had a consistent inhibitory effect on FSH-stimulated granulosa cell cAMP formation either in the presence or absence of 1-methyl-3-isobutyl-xanthine (MIX); but during the 2-day culture, ICI-118630 and occasionally LHRH significantly inhibited aromatase induction by cholera toxin and 2 different cAMP analogues. Over the same range of concentrations, each peptide progressively inhibited the stimulatory effect of MIX on FSH-induced aromatase activity and progestogen biosynthesis. Thus LHRH/ICI-118630 can directly modulate FSH-controlled granulosa cell steroidogenesis in vitro via effects on one or more biochemical loci distal to the FSH-receptor coupled adenylate cyclase system. These experiments have implications for the role of a putative LHRH-like ovarian substance(s) in the local co-ordination of follicular development and function.
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017273:Goserelin; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000096:biosynthesis*
D013256:Steroids; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D001141:Aromatase