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 cytotrophoblasts aggregated and fused to form syncytia. This morphological transformation was not affected by 8-bromo-cAMP. Immunocytochemical studies of the alpha- and beta-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 cytotrophoblasts did not aggregate or form syncytia, yet they responded to 8-bromo-cAMP with an increase in hCG secretion. We conclude 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.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000096:biosynthesis / Q000378:metabolism*; D006651:Histocytochemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D011374:Progesterone / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone