Transforming growth factor-beta 1 and -beta 2 induce inhibin and activin beta B-subunit messenger ribonucleic acid levels in cultured human granulosa-luteal cells.

OBJECTIVE: To examine the effect of transforming growth factor-beta (TGF-beta) on inhibin and activin subunit messenger ribonucleic acids.
DESIGN: Human granulosa-luteal cell culture model.
SETTING: Granulosa cells were obtained from women undergoing an IVF program in a private IVF clinic. PATIENTS: Regularly menstruating women undergoing oocyte retrieval for IVF because of either tubal obstruction or infertility of the spouse.
INTERVENTIONS: 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.
RESULTS: 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.
CONCLUSIONS: 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.