COMPARATIVE REGULATION OF INHIBIN, ACTIVIN AND HUMAN CHORIONIC-GONADOTROPIN PRODUCTION BY PLACENTAL TROPHOBLAST CELLS IN CULTURE

In the present study, we investigated the roles of cyclic adenosine mo nophosphate (cAMP), intracellular calcium, glucocorticoids, protein ki nase-C and gonadotrophin-releasing hormone (GnRH) in regulating human chorionic gonadotrophin (hCG), inhibin and activin production in cultu red human term placental trophoblast cells. Inhibin and hCG mere measu red in conditioned media by radioimmunoassay, while putative forms of inhibin and activin mere characterized by, western blotting using affi nity-purified antisera directed against the inhibin alpha- and beta A- subunits. Inhibin and hCG secretion mere stimulated by dexamethasone ( 0.2 mu M), GnRH (5-25 mu M), calcium ionophore A23187 (0.2-1 mu M), ph orbol-12-myristate-13-acetate (22 nM) and epinephrine (1 mu M), with i ncreasing response over successive 24-h treatment periods. Two molecul es Mr similar to 30 and 32 kDa appeared to be the predominant dimeric forms of inhibin secreted by the cells, while 26 kDa activin was prese nt in excess over inhibin. Large amounts of 40-44 kDa protein were det ected by the alpha-directed antisera only, which may be a form of the inhibin alpha-subunit precursor protein. Secretion of activin was resp onsive to phorbol ester mediated stimulation but not to the presence o f GnRH or elevated cAMP concentrations. The divergence in maternal ser um inhibin and hCG concentrations during late pregnancy remains unexpl ained by these findings.