Induction of 17α-hydroxylase (cytochrome P-450 17 α) activity by adrenocorticotropin in bovine adrenocortical cells maintained in monolayer culture

Abstract

Using bovine adrenocortical cells in monolayer culture it has been shown that treatment with adrenocorticotropin (ACTH) causes a dramatic increase in 17α-hydroxylase activity. In postmitochondrial supernatant fractions (PMS) prepared from cells maintained in culture, there was a 15-fold increase in 17α-hydroxylase activity 36 h following initiation of ACTH treatment compared with the activity measured in PMS prepared from control cells. In the continued presence of ACTH, 17α-hydroxylase activity declined; however, even after 60 h of exposure to ACTH, 17α-hydroxylase activity was eight times higher than that present in control cells. The dramatic increase in 17α-hydroxylase activity provides an explanation for the previously observed phenomenon that following initiation of ACTH treatment of bovine adrenocortical cells in monolayer culture there is a shift in the pattern of corticosteroid secretion from approximately equal amounts of cortisol and corticosterone to almost exclusively cortisol. Thus, the modulation of 17α-hydroxylase activity by ACTH action appears to serve a key regulatory role in the pattern of corticosteroid production. Soluble cytosolic factors apparently do not participate in the regulation of 17α-hydroxylase activity in the bovine adrenal cortex. Increases in the magnitude of substrate-induced absorbance changes are indicative that the increase in 17α-hydroxylase activity is due, at least in part, to an elevation of cytochrome P-450 17 α synthesis.