Control of the steroidogenic machinery of the human trophoblast by cyclic AMP.

Abstract

Human cytotrophoblasts express adenylate cyclase activity and possess membrane-bound regulatory proteins that bind guanine nucleotides (G proteins). Stimulation of the cyclase by forskolin or addition of 8-bromo-cAMP augments progesterone secretion by cultured cytotrophoblasts at least in part, by promoting accumulation of components of the cholesterol side-chain cleavage system. This is the consequence of increased synthesis of the proteins participating in steroidogenesis as a result of the 8-bromo-cAMP-provoked increase in their respective mRNAs. We propose that progesterone synthesis by cytotrophoblasts is up-regulated by cyclic AMP, which acts to increase expression of genes encoding the steroidogenic machinery. Paracrine or autocrine factors may initiate this cascade by stimulating the cytotrophoblast adenylate cyclase.