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

Departments of Obstetrics and Gynecology Philadelphia, Pennsylvania 19104
Pathology and Laboratory Medicine University of Pennsylvania School ofMedicine Philadelphia, Pennsylvania 19104
Physiology University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Jerome F. Strauss III, M.D., Ph.D., Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Phil-adelphia, Pennsylvania 19104.

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 - 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.

^* This work was supported by USPHS Grant HD-06274 (to J.F.S.), HD-00715 (to H.J.K.), a grant from the Mellon Foundation (to M.A.F.) and a grant from the Diabetes Research and Education Foundation (to H.J.K.).

Received February 20, 1986.

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