Effects of 31 kDa bovine inhibin on FSH and LH in rat pituitary cells in vitro: antagonism of gonadotrophin-releasing hormone agonists.
The effects of 31 kDa bovine inhibin on the release of FSH and LH stimulated by gonadotrophin-releasing hormone (GnRH) or its agonist analogue buserelin have been studied using 5-day-old cultures of pituitary cells prepared from adult male Sprague-Dawley rats. Exposure of cultures to increasing concentrations of inhibin for 3 days before and during a 4-h stimulation with GnRH resulted in the progressive suppression of both basal and stimulated gonadotrophin release. At the highest inhibin concentrations FSH release was abolished (inhibin median inhibitory concentration (IC50) = 0.15 U/ml) whereas LH release was suppressed by 75% (IC50 = 0.93 U/ml). To correct for the reduced size of the FSH pool resulting from inhibin pretreatment, the amount of FSH or LH released by an agonist was expressed as a proportion of the total hormone available for release in each case. Following this adjustment, concentrations of inhibin producing maximal effects increased the GnRH median effective concentration for FSH release 4.1-fold and that for LH release 2.2-fold, with inhibin IC50 values of 0.45 and 0.32 U/ml respectively. Inhibin also suppressed the maximum proportion of both FSH and LH that excess GnRH released in 4 h by 36%, with IC50 values of 0.53 and 0.76 U/ml respectively. These effects were not changed by reduction of the inhibin pretreatment period from 3 days to 1 day or by exclusion of inhibin during the stimulation period. After a 3-day pretreatment, inhibin inhibited gonadotrophin release by buserelin less effectively than that by GnRH, but the pattern of antagonism was the same.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007265:Inhibins / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010906:Pituitary Hormone-Releasing Hormones; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone