Differential regulation of hCG and progesterone secretion by cholera toxin and phorbol ester in human cytotrophoblasts

The secretion of hCG and progesterone (P) by human cytotrophoblasts was studied in response to cholera toxin (CT), which activates adenylate cyclase, and 12-0-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C stimulator. During a 24 h incubation CT and TPA increased hCG and P secretion in a concentration-dependent manner. At maximal effective concentrations, CT (1.0 ng/ml), TPA (10 ng/ml) and CT plus TPA stimulated hCG production by 5.7-, 2.7- and 10.0-fold, respectively, and P production by 1.8-, 1.8- and 2.0-fold, respectively. Time-course studies indicated that these effects became detectable after 12 h and increased up to 48 h of incubation. During a 24 h culture TPA potentiated CT-induced cAMP formation by 1.4-fold indicating that its effects on hCG production may be, at least partly, mediated through cAMP. In conclusion, CT and TPA are potent stimulators of human cytotrophoblast hCG and P production. Simultaneous stimulation by these agents results in potentiation of hCG production whereas P production remains at the same level as with CT or TPA alone. The results suggest that the endocrine activity of human cytotrophoblasts is under multihormonal control and hCG and P secretion are differentially regulated.