Transforming growth factor-β1 and -β2 induce inhibin and activin βB-subunit messenger ribonucleic acid levels in cultured human granulosa-luteal cells

Abstract

To examine the effect of transforming growth factor-beta (TGF-beta) on inhibin and activin subunit messenger ribonucleic acids. Human granulosa-luteal cell culture model. Granulosa cells were obtained from women undergoing an IVF program in a private IVF clinic. Regularly menstruating women undergoing oocyte retrieval for IVF because of either tubal obstruction or infertility of the spouse. For each experiment, cells of two to four patients were pooled, enzymatically dispersed, separated from red blood cells by centrifugation through Ficoll-Paque and cultured in vitro in the presence of TGF-beta 1 or TGF-beta 2 and/or hCG whereafter cellular RNA was extracted for Northern or dot blot filter hybridization with inhibin alpha-, beta A, and beta B-subunit complementary DNA probes. Both TGF-beta 1 and TGF-beta 2 induced the expression of a 4.8-kb inhibin and activin beta B-subunit messenger (mRNA) transcript in a time- and dose-dependent manner but had no effect on alpha- or beta A-subunit mRNA levels. Human chorionic gonadotropin alone did not affect beta B-subunit mRNA levels, but when administered together with TGF-beta s, it prevented the induction of beta B-subunit mRNAs. Our results suggest that in human ovary, granulosa, or thecal cell-derived TGF-beta 1 or -beta 2 may eventually locally modulate in a paracrine or autocrine manner the relative expression levels of inhibin and activin subunits favoring the formation of the inhibin and activin dimers containing the beta B-subunit. The effect of TGF-beta is clearly different from that of gonadotropins, which potently induce the alpha- and beta A-subunit mRNAs, indicating that distinct components of the human ovarian inhibin and activin system are regulated differentially by endocrine and local factors.