STUDIES ON CYCLIC NUCLEOTIDES IN THE ADRENAL GLAND

Abstract

Effects of ACTH and Ca on cyclic[c]AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex were studied. Increasing concentrations of extracellular Ca enhanced the action of ACTH on cAMP and steroid production. These effects of ACTH with Ca were prevented by lanthanum but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by Ca through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the Ca current. High concentrations of external Ca itself increased cAMP accumulation without any increase in steroidogenesis. A Ca ionophore, X537A, was stimulatory for steroidogenesis but inhibitory with respect to cAMP accumulation. Considered together with the findings of steroidogenic stimulation by low concentrations of ACTH without cAMP increase, these results suggest, that ACTH primarily increases intracellular Ca mobilization thus directly stimulating steroidogenesis, which is independent of the cAMP system. Relatively high concentrations of ACTH activate adenylate cyclase, which depends on extracellular Ca to increase cAMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.