Effects of sodium nitroprusside and ascorbic acid on rat adrenocortical cell cGMP levels and steroidogenesis

Cyclic GMP levels in isolated rat adrenocortical cells were not significantly altered by ACTH (5 or 250 μU/ml), although cAMP levels were increased by 60-fold in response to 250 μU of ACTH after 30 min of incubation. Corticosterone production by adrenocortical cells was increased 13- and 23-fold by 5 and 250 μU/ml of ACTH, respectively. When cells were incubated in the presence of sodium nitroprusside (0.01-1 mM), they responded with concentration- and time-dependent increases in cGMP levels of up to 20-fold after 30 min of incubation. Adrenocortical cell cGMP levels were also increased by 2-fold in response to 2.5 or 10 mM ascorbic acid during 30 min of incubaton. cAMP levels were not changed in response to either nitroprusside or ascorbic acid. Neither nitroprusside nor ascorbic acid, in concentrations which increased cGMP levels, altered basal levels of corticosterone production or the increased steroid synthesis elicited by pregnenolone. In addition, ACTH-induced increases in corticosterone production were either not changed or slightly depressed by nitroprusside or ascorbic acid. Thus, adrenocortical cell steroidogenic capacity and responsivity were largely preserved during exposure to nitroprusside or ascorbic acid. These data indicate that inceased levels of cGMP are not a sufficient stimulus for adrenocortical steroidogenesis. Moreover, since ACTH can stimulate steroidogenesis in the absence of detectable changes in cGMP levels, and since pharmacologically-increased levels of cGMP do not increase submaximal ACTH-stimulated corticosterone production, cGMP does not appear to be a mediator of ACTH effects on steroidogenesis.