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

Arch Biochem Biophys. 1983 Apr 15;222(2):590-8. doi: 10.1016/0003-9861(83)90557-x.

Abstract

Using bovine adrenocortical cells in monolayer culture it has been shown that treatment with adrenocorticotropin (ACTH) causes a dramatic increase in 17 alpha-hydroxylase activity. In postmitochondrial supernatant fractions (PMS) prepared from cells maintained in culture, there was a 15-fold increase in 17 alpha-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, 17 alpha-hydroxylase activity declined; however, even after 60 h of exposure to ACTH, 17 alpha-hydroxylase activity was eight times higher than that present in control cells. The dramatic increase in 17 alpha-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 17 alpha-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 17 alpha-hydroxylase activity in the bovine adrenal cortex. Increases in the magnitude of substrate-induced absorbance changes are indicative that the increase in 17 alpha-hydroxylase activity is due, at least in part, to an elevation of cytochrome P-450(17)alpha synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex / enzymology*
  • Adrenocorticotropic Hormone / pharmacology*
  • Animals
  • Cattle
  • Cells, Cultured
  • Corticosterone / biosynthesis
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Induction / drug effects
  • Hydrocortisone / biosynthesis
  • Steroid 17-alpha-Hydroxylase / biosynthesis*
  • Steroid Hydroxylases / biosynthesis*

Substances

  • Adrenocorticotropic Hormone
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Steroid 17-alpha-Hydroxylase
  • Corticosterone
  • Hydrocortisone