Synergistic effects of chymotrypsin and human chorionic gonadotrophin on rat luteal adenylate cyclase.

The effects of chymotrypsin on rat luteal adenylate cyclase have been investigated. Maximal stimulation occurred at a concentration of 10 micrograms/ml. This dose of chymotrypsin stimulated basal, GTP-,5'-(beta, gamma-imido)triphosphate-, and NaF-stimulated adenylate cyclase activity 2- to 3-fold. hCG-stimulated activities were stimulated 5- to 6-fold by the proteinase and showed a synergistic effect. The proteinase did not alter the hCG response curve, and the effect could not be mimicked by trypsin. Proteolytic activity was required, since chymotrypsinogen and inactivated chymotrypsin were not effective. The presence of chymotrypsin could not restore the hormonal sensitivity of a proteinase inhibitor-inactivated system. The results suggest that chymotrypsin stimulated rat luteal adenylate cyclase activity by two or more mechanisms: 1) a direct action on the catalytic subunit or a closely associated protein, and 2) an action somewhere in the pathway of hormonal stimulation.