Effect of adrenocorticotropin on steroid 21-hydroxylase synthesis and activity in cultured bovine adrenocortical cells. Increased synthesis in the absence of increased activity

J Biol Chem. 1983 Aug 10;258(15):9398-405.


The action of adrenocorticotropin (ACTH) to stimulate synthesis of steroid 21-hydroxylase was studied in bovine adrenocortical cells maintained in primary culture. Continuous treatment with ACTH (1 microM) caused an increased incorporation of [35S]methionine into cytochrome P-450C21 (21-hydroxylase cytochrome P-450); a maximum value (15-fold increase) was attained 24 h after initiation of ACTH treatment. Also, a 3-fold increase in cytochrome P-450C21 synthesis was observed in a cell-free translation system programmed by RNA isolated from cells that were exposed to ACTH for 24 h. The rate of synthesis of cytochrome P-450C21 declined after longer periods of treatment of the cells with ACTH. The increase in synthesis of cytochrome P-450C21 was associated with an increase (3-6 fold) in both total cytochrome P-450 content and in the type I absorbance change induced by 17 alpha-hydroxyprogesterone in microsomes prepared from ACTH-treated cells, as compared with that in microsomes from control cells. By contrast, ACTH did not act to increase steroid 21-hydroxylase activity in cultured intact cells, as determined by the rate of secretion of cortisol and 11-deoxycortisol, after addition of 17 alpha-hydroxyprogesterone to the medium. Similarly, there was no difference in steroid 21-hydroxylase activity in postmitochondrial supernatant fractions prepared from non-treated or ACTH-treated cells. Cytochrome P-450C21 was found to be synthesized as a form identical in molecular weight to the mature form. These results are indicative that ACTH acts to stimulate the synthesis of steroid 21-hydroxylase, yet is without a demonstrable effect on the activity of this enzyme which is high throughout the time period of the experiment.

Publication types

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

MeSH terms

  • Adrenal Cortex / drug effects
  • Adrenal Cortex / enzymology*
  • Adrenocorticotropic Hormone / pharmacology*
  • Animals
  • Cattle
  • Cell-Free System
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Induction
  • Steroid 21-Hydroxylase / biosynthesis*
  • Steroid Hydroxylases / biosynthesis*


  • Adrenocorticotropic Hormone
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Steroid 21-Hydroxylase