Pharmacologically induced changes in human beta-chorionic gonadotropin (beta-hCG) synthesis by human placenta in...

In organ cultures the regulation of beta-hCG formation in human placentas of early gestation (EG) and at term (T) was analyzed using the following test substances: dibutyryl cAMP (dbcAMP), theophylline, and by two drugs used to treat patients with premature labor, fenoterol hydrobromide and verapamil hydrochloride. The rapid increase in beta-hCG in culture medium beginning at 24-48 h corresponds to morphologic changes (proliferation of the cytotrophoblast). Beta-hCG synthesis of human placenta is related to an adenylate cyclase as could be shown by dose-dependent stimulation by dbcAMP (T) (after 72 h) (controls = 100%): 2 nM = 125%; 70 nM = 200%; 2 microM = 300%. Similar results were obtained using EG. First stimulation by dbcAMP was found after 2 h and may be caused by a release of intracellular beta-CG or by a direct stimulation of beta-hCG synthesis; late effects (after 48-72 h) are suspected to be due to changes in morphologic differentiation of the placenta in organ culture. Theophylline (0.1 and 1 mM) did not influence beta-hCG formation in EG, whereas in T a dose-dependent stimulation could be achieved (controls = 100%): 0.1 mM = 110%; 1 mM = 300%; and 10 mM = 160%. Fenoterol hydrobromide, a tocolytic beta 2-receptor stimulating agent showed a slight (130-160%) beta-hCG stimulation (after 72 h) (EG and T). The stimulatory effect of a high dose (1 microgram/ml) of fenoterol hydrobromide could be due to a stimulation of beta 2 receptors related to an adenylate cyclase. Dose-related changes in beta-hCG in T were found for the calcium antagonist verapamil hydrochloride (controls = 100%): 0.01 microgram/ml = 125% stimulation; 0.33 microgram/ml = 200% stimulation; 10 micrograms/ml = 100%. As indicated by verapamil tests, calcium ions may play a role in the regulation of beta-hCG production.