Effect of Recombinant Inhibin on Follicle-Stimulating Hormone Secretion by the Female Rat: Interaction with a Gonadotropin-Releasing Hormone Antagonist and Estrogen*

There is considerable support for the hypothesis that one component of FSH secretion is independent of GnRH. The ability of follicular fluid preparations containing inhibin to suppress FSH release in the absence of GnRH drive has suggested that this component might be responsive to gonadal proteins. However, follicular fluid contains several proteins that either stimulate or inhibit FSH secretion, thus complicating interpretation of the results. The recent availability of recombinant human (rh) inhibin-A has allowed us to specifically investigate the effect of this protein on FSH secretion by rats whose GnRH release and/or effect was blocked by a specific antagonist, (Ac-D2Nall,DCpa2,D3Pa13,Arg6,D5-(p-methoxypheny)) 5-oxo-2-aminopentanoic acid6,DAlal0]GnRH, or by estradiol (E2). In a first experiment, the GnRH antagonist (100 μg/kg, injected sc 21 h earlier) lowered plasma immunoactive FSH levels by 36%, and rh- inhibin -A (25μ g/kg, injected iv 6 h earlier) lowered them by 44%. The combination of both treatments decreased FSH values by 82% (P ≤ 0.01 us. either compound alone). Inhibin and the antagonist also significantly (P ≤ 0.01) decreased FSH bioactivity. A second experiment investigated the independent or combined effects of inhibin and E2. E2 (40 μg/kg, injected scat -36 and -12 h) lowered FSH levels by 53%, and inhibin (25 μg/kg, injected iv at —6 h) decreased FSH concentrations by 37%. Administration of both compounds produced a 63% inhibition (P ≤ 0.05 us. inhibin alone; P ≤ 0.01 us. E2 alone). Finally, we studied the interaction among the GnRH antagonist, inhibin, and E2, In this protocol plasma FSH levels in rats injected with inhibin and the antagonist did not show an additional decrease after treatment with E2. These results indicate that plasma FSH levels in rats whose GnRH receptors or secretion are blocked can be further lowered by inhibin. Thus, the ability of rh-inhibin-A to interfere with FSH secretion in the ovariectomized rat appears to involve a mechanism independent of the GnRH drive. (Endocrinology129: 2160–2165,1991)