BETA-ADRENERGIC REGULATION OF CYCLIC-AMP SYNTHESIS IN CULTURED HUMAN SYNCYTIOTROPHOBLAST

Isolated elements of the beta-adrenergic/adenyl cyclase signal transdu ction system have been studied previously using purified membranes. We used cultured syncytiotrophoblast cells to identify components of thi s signalling system and the interactions which regulate syncytial aden yl cyclase. Generation of cyclic AMP (cAMP) was stimulated in these ce lls by both forskolin and isoproterenol but not by dopamine, adenosine , carbachol or prostaglandin E(1). Synthesis was also stimulated by tr eatment with cholera toxin, indicating the involvement of the G-protei n, G(s). Somatostatin inhibited isoproterenol- or forskolin-stimulated cAMP generation, an effect which could be blocked by pretreatment of the cells with pertussis toxin, demonstrating the mediation of somatos tatin action by G(i). Furthermore, secretion of human chorionic gonado trophin (hCG) was increased significantly by isoproterenol while somat ostatin blocked the isoproterenol-stimulated release of hCG. These res ults clearly demonstrate that adenyl cyclase in syncytiotrophoblast is controlled by a stimulatory pathway operating through G(s) and inhibi tory pathway, acting through G(i).