Independent Dibutyryl Cyclic Adenosine Monophosphate Stimulation of Human Chorionic Gonadotropin and Estrogen Secretion by Malignant Trophoblast Cellsin Vitro

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Abstract
Human malignant trophoblast cells in continuous culture were employed to investigate the causal relationship between N6,O2′-dibutyryl cyclic adenosine 3′,5′-monophosphoric acid. (dbcAMP) stimulation of human chorionic gonadotropin (hCG) secretion and dbcAMP stimulation of estrone and 17β-estradiol (E) secretion. The cells secreted up to 25 times more hCG when propagated in medium containing 10% serum, compared to growth in the absence of serum. By contrast, serum had little effect on E secretion. In the presence of serum, dbcAMP resulted in marked stimulation of hCG and E secretion; both processes were potentiated by theophylline. When cells were incubated with various concentrations of dbcAMP or theophylline, stimulation of hCG secretion was disproportionately greater than the stimulation of E secretion. Furthermore, the relative stimulation of secretion of the two hormones was not constant. The rate of hCG, but not of E, secretion was elevated for at least 2 days following a 7-hr pulse with dbcAMP. Cells treated with dbcAMP for 2–3 days in the absence of serum, “primed cells”, secreted levels of E which were only slightly higher than control levels but amounts of hCG some 16 times that in control cultures. Addition of serum to primed cells was followed by a rapid increase in both hCG and E secretion; cycloheximide prevented the rise in hCG but npt in E secretion. We conclude that enhanced secretion of hCG and E by dbcAMP are separate events.

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