Inhibition of FSH-stimulated granulosa cell function by a synthetic fragment of the porcine inhibin alpha-subunit: evidence for involvement of GnRH receptors.
The bioactivity of a synthetic peptide fragment which mimics the N-terminal sequence of the 134-amino-acid porcine inhibin alpha-subunit (pl-alpha 1-26-Gly27Tyr28-OH) was tested and compared with the bioactivity of GnRH in rat granulosa cell cultures. Granulosa cells from immature female rat ovaries were cultured with hFSH and testosterone to stimulate the production of cyclic AMP, progesterone and oestradiol. Addition of pl-alpha 1-26-Gly27Tyr28-OH to the culture medium caused a dose-dependent suppression of all three parameters (ID50 700-1,000 nmol/l). GnRH caused similar but higher-potency inhibition (ID50 2-4 nmol/l). Suppression of granulosa cell function by both peptides was fully reversible by a synthetic GnRH antagonist. Moreover, specific binding of the porcine inhibin fragment to ovarian GnRH receptors was demonstrated by radioreceptor assay. This is evidence that the porcine inhibin alpha-subunit fragment suppresses FSH-induced rat granulosa cell function via a mechanism of action similar to that of GnRH.
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007265:Inhibins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011966:Receptors, LHRH / Q000032:analysis
D010446:Peptide Fragments; D010906:Pituitary Hormone-Releasing Hormones; D011966:Receptors, LHRH; D011374:Progesterone; D004958:Estradiol; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP