8-Bromo-3′5′ -Adenosine Monophosphate Stimulates the Endocrine Activity of Human Cytotrophoblasts in Culture

Cytotrophoblasts, purified from human term placentae, were cultured in the absence or presence of 8-bromo- cAMP or 8-bromo-cGMP. 8-Bromo-cAMP provoked a dose- dependent increase in the secretion of hCG and progesterone within 24 h. After 48 h, hCG secretion increased by more than 200-fold, and progesterone secretion increased nearly 5-fold. 8- Bromo-cGMP had no effect on hCG secretion. In culture in serum-supplemented medium, the mononuclear cytotrophd- blasts aggregated and fused to form syncytia. This morphological transformation was not affected by 8-bromo-cAMP. Immuno- cytochemical studies of the a- and /3-subunits of hCG in control and 8-bromo-cAMP-stimulated cultures demonstrated that the cyclic nucleotide analog promoted the synthesis of both subunits in all cellular forms, including single mononuclear cells, cell aggregates, and syncytia. In serum-free medium, the cytotroph- oblasts did not aggregate or form syncytia, yet they responded to 8-bromo-cAMP with ah increase in hCG secretion. We con- clude that the endocrine function of cytotrophoblasts can be stimulated by a cAMP-dependent mechanism which can be initiated independently of the formation of a syncytium. (