Suppression of Basal and GnRH-Stimulated Gonadotropin Secretion Rate in vitro by GnRH Antagonist: Differential Effects on Metestrous and Proestrous Pituitaries

Abstract

LH and FSH basal secretion rates (BSR) in vitro of pituitary fragments from female rats at metestrus or following ovariectomy parallel changes seen in serum gonadotropins. These findings led us to suspect that in vitro BSR of fragments depended on prior exposure to GnRH or lingering GnRH in the culture. We compared pituitaries removed from rats in two cycle stages, proestrus (PRO) and metestrus (MET). Rats were given a single injection of a potent GnRH antagonist, Antag-WY 45760-[Ac-beta(2)-D-Nal1,4-F-D-Phe2,D-Trp3,D-Arg6]-LHRH, or oil prior to sacrifice at 09.00 h on PRO or MET. Pituitary fragments were perifused for 8 h. To test the effects of Antag in vitro some pituitaries from oil-injected rats were perifused with medium containing 1 microM Antag for the first 4 h. Starting at 5 h all chambers received hourly 10-min pulses of 1 microM GnRH. In PRO rats Antag injection in vivo lowered LH BSR to 50% and FSH to 70% of oil-treated controls. Surprisingly, Antag administered in vitro suppressed LH BSR to 30% and FSH to 55% of controls. In pituitaries from MET rats, BSR or LH and FSH were 20 and 70% of control PRO values and were unaffected by Antag treatment in vivo or in vitro. In PRO pituitaries LH and FSH responses to the first GnRH pulse were blunted by Antag in vivo but responses to subsequent pulses were unaffected; MET responses were not different from controls. In vitro Antag suppressed GnRH-stimulated release to 10-20% of controls at both cycle stages.(ABSTRACT TRUNCATED AT 250 WORDS)