Effects of Butyrate and Dibutyryl Cyclic AMP on hCG-secreting Trophoblastic and Non-trophoblastic Cells*

Publisher Website
Google Scholar
Abstract
The ability of N6,O2’-dibutyryl cyclic 3’:5’ AMP (dbcAMP) plus theophylline (T) to stimulate the secretion of hCG and its α and /β subunits was compared with the effect of butyrate in short-term explants of human placenta, in human malignant trophoblastic cultures (BeWo and JAr lines), and in three human malignant non-trophoblastic cell lines. The non-trophoblastic cultures included the EICo (established in 1973 from breast carcinoma and a producer of hCGa), CaSki (established in 1974 from cervical carcinoma and a producer of hCG/β), and DoT (established in 1974 and a producer of hCG/β) cell lines. Butyrate (0.01—5 HIM) did not stimulate the secretion of hCG or its subunits in the BeWo or JAr trophoblastic cells. In incubations with placental explants, 0.2—5 mM butyrate caused only a 1.5- to 2.5-fold stimulation of hCG secretion. By contrast, 5 mM butyrate stimulated secretion of hCGa (EICo) and hCG/8 (DoT) by 14 to 24 times (expressed per milligram of cell protein). The effects of dbcAMP and T on secretion of hCG and its subunits were essentially reversed, compared with the effects of butyrate, in both the trophoblastic and non-trophoblastic cells. Thus, 1 mM dbcAMP plus 1 mM T caused dramatic (up to 250-fold) stimulation of hCG and both subunits in incubations with trophoblastic cells or placenta, but caused less than 2-fold stimulation of hCG/J secretion by CaSki or DoT cells. In EICo cells, dbcAMP plus T increased the secretion of hCGa by approximately six times. These findings suggested that regulation of the secretion of hCG and its subunits in the trophoblast may differ from the mechanism in non-trophoblastic cells.