ACTIVIN-A STIMULATES, WHILE TRANSFORMING GROWTH-FACTOR BETA(1) INHIBITS, CHORIONIC-GONADOTROPIN PRODUCTION AND AROMATASE-ACTIVITY IN CULTURED HUMAN PLACENTAL TROPHOBLASTS

Transforming growth factor-beta (TGF-beta) and activin-A, two members of a ubiquitous family of regulators of growth, differentiation and ho rmonogenesis, are produced by the human placenta. Their effects on pla cental hCG, inhibin, and oestrogen production in vitro, either alone o r in combination, were investigated using cultured Percoll-purified pl acental trophoblasts. Inhibin and hCG were measured by immunoassay, wh ile aromatase activity (i.e. oestrogen production) was measured using the tritiated water method. Aromatase activity and production of hCG, but not inhibin, were inhibited (up to similar to 30 per cent) in a do se-dependent fashion by 48 h treatment with TGF-beta. The effects were significant at all doses tested, from 0.1-10 ng/ml. In contrast, acti vin stimulated hCG production and aromatase activity over the doses te sted (0.25-25 ng/ml). The maximum effect (similar to 50 per cent stimu lation above control) was seen at the 2.5 ng/ml dose, with lesser effe cts seen at the lower and higher doses. This characteristic bell-shape d dose-response curve was maintained in the presence of TGF-beta (10 n g/ml) or a maximally-effective dose of forskolin (6.7 mu M). This sugg ests that the actions of activin were independent of those of TGF-beta , and were not mediated by the protein kinase-A pathway. Activin had a weak stimulatory effect on inhibin production. The results indicate t hat in the placenta activin and TGF-beta have opposing actions on horm onogenesis. Both factors may play a role in regulating placental funct ion and the timing and progression of labour. (C) 1996 W. B. Saunders Company Ltd