Comparison of the effects of crude and highly purified bovine inhibin (Mr 32 000) on plasma concentrations of FSH and LH in chronically ovariectomized prepubertal heifers

Abstract

ABSTRACT Chronically ovariectomized prepubertal heifers were used for a comparison of the effects of highly purified bovine inhibin (Mr 32 000) and steroid-free bovine follicular fluid (bFF) on the secretion of FSH and LH. In view of the limited availability of highly purified inhibin, an initial study was undertaken to establish the optimal method for administration of bFF inhibin activity. In comparison with the FSH response to a single large i.v. bolus injection of bFF (50 ml; 3250 mg protein), a far more effective suppression of plasma FSH concentrations was achieved when considerably less bFF (6·3 ml; 410 mg protein) was administered gradually over an extended time-period (2 days) either as a continuous i.v. infusion or as a series of 2-hourly i.v. injections. Following a single i.v. bolus injection of bFF, immunoreactive inhibin was cleared rapidly from the circulation (half-life 51 ± 8 (s.e.m.) min, n = 5), presumably accounting for its limited ability to suppress FSH secretion when administered in this manner. In a second experiment, treatment of ovariectomized heifers (three per group) with highly purified Mr 32 000 bovine inhibin at a dose rate of 15 μg/2 h for 2 days significantly (P < 0·05) suppressed plasma FSH concentrations, which reached their minimum values (40% suppression) during day 2 of treatment. At a lower dose rate (5 μg/2 h), inhibin did not significantly affect plasma FSH levels. Administration of bFF was also associated with a dose-dependent suppression of FSH secretion. For each of three dose rates tested (three heifers per group), plasma FSH concentrations were maximally suppressed during day 2 of treatment (65 mg/2 h, 86% suppression, P < 0·001; 21·7 mg/2 h, 66% suppression, P < 0·001; 7·2 mg/2 h, 15% suppression, P > 0·05). Neither highly purified inhibin nor bFF significantly affected mean plasma LH concentrations, LH pulse frequency or LH pulse amplitude. Thus we have shown for the first time that highly purified Mr 32 000 bovine inhibin does possess in-vivo biological activity in cattle, promoting a selective suppression of plasma FSH concentrations qualitatively similar to that evoked by steroid-free bFF. Quantitatively, the inhibin preparation had an in-vivo biopotency about 1000 times greater than that of bFF, a value which accords well with its biopotency (1176 × bFF) in the in-vitro rat pituitary cell bioassay. Journal of Endocrinology (1990) 125, 21–30