TRANSFORMING GROWTH-FACTOR-BETA-1 AND GROWTH FACTOR-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 (T GF-beta) on inhibin and activin subunit messenger ribonucleic acids. D esign: Human granulosa-luteal cell culture model. Setting: Granulosa c ells were obtained from women undergoing an IVF program in a private I VF clinic. Patients: Regularly menstruating women undergoing oocyte re trieval for IVF because of either tubal obstruction or infertility of the spouse. Interventions: For each experiment, cells of two to four p atients 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 cellul ar RNA was extracted for Northern or dot blot filter hybridization wit h inhibin alpha-, beta(A), and beta(B)-subunit complementary DNA probe s. 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) transcrip t in a time- and dose-dependent manner but had no effect on alpha- or beta(A)-subunit mRNA levels. Human chorionic gonadotropin alone did no t affect beta(B)-subunit mRNA levels, but when administered together w ith TGF-beta s, it prevented the induction of beta(B)-subunit mRNAs. C onclusions: Our results suggest that in human ovary, granulosa, or the cal 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 induc e the alpha- and beta(A)-subunit mRNAs, indicating that distinct compo nents of the human ovarian inhibin and activin system are regulated di fferentially by endocrine and local factors.