Production and actions of inhibin and activin during folliculogenesis in the rat

Evidence to enhance the premise that inhibin and activin are local regulato rs of ovarian folliculogenesis is presented in this review. Granulosa cells (GC) have been identified as the source of inhibin, activin in the ovary o n the basis of mRNA and protein localisation and the measurement of the inh ibin forms in GC conditioned media, Expression of the subunit mRNAs changed with follicular development, being maximal in the ovaries of 8-day-old rat s., where secondary follicles predominate. The expression of beta subunit m RNAs by GC isolated front diethylstilboestrol (DES)-treated immature rats. was reduced in the absence of any change in alpha subunit mRNA expression. Dimeric inhibin-A, -B and free alpha subunit were produced by ovarian cell cultures prepared from 4- to 12-day-old rats. Inhibin-A production by these cultures was responsive to FSH and TGF-beta. with preantral follicles of d ay 8 ovaries exerting effects so profound that the inhibin A/alpha subunit ratio increased, most likely due to a stimulation of beta (A) subunit produ ction. In contrast, inhibin-B was not stimulated by TGF-beta until day 8 an d FSH until day 12. Fractionation of GC conditioned media revealed a promin ence of free alpha subunit and inhibin-A, but little inhibin-B, suggesting that inhibin-B production declines with follicular development. Activin rec eptor types I and II, Smads 1-8 and betaglycan (beta -glycan) mRNAs were pr esent in the rat ovary and showed distinct patterns of expression between p ostnatal days 4 and 12. Oocytes and GC localised activin receptor, Smad and beta -glycan proteins, with beta -glycan also present in theca cells (TC). These data indicate that activin/TGF-beta signalling machinery and factors which influence these pathways, are present in the postnatal rat ovary. Ou r hypothesis that inhibin and activin play important and changing autocrine /paracrine roles in the growth and differentiation of follicles, including the oocyte, has been supported by these Studies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.