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

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Abstract
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 α- and β-subunits of hCG in controland 8-bromo-cAMP-stimulated cultures demonstrated that the cyclic nucleotide analog promoted the synthesis of both subunits n i 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 t o 8-bromo-cAMP with ah 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.

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