Transforming growth factor-beta inhibits steroid 17 alpha-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells

Endocrinology. 1990 Oct;127(4):1910-5. doi: 10.1210/endo-127-4-1910.


The maintenance of optimal steroidogenesis in adrenocortical cells primarily depends on the chronic action of ACTH to promote the synthesis of the various steroid-metabolizing cytochrome P-450 enzymes. In the steroidogenic pathway, 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) is a key enzyme controlling the formation of cortisol and androgens. Recently, we demonstrated that transforming growth factor-beta (TGF beta) is a potent inhibitor of steroid production in ovine adrenocortical cells. In the present study we used a polyclonal antibody to P450(17) alpha to determine adrenal cell P-450(17) alpha enzyme content by Western analysis. In addition, we used a cDNA probe encoding for bovine P-450(17) alpha mRNA to determine levels of P-450(17) alpha mRNA in sheep ovarian adrenocortical cells in primary culture. When cells were cultured in a serum-free medium in the presence of ACTH for 48 h, P-450(17) alpha activity, enzyme content, and mRNA levels for P-450(17) alpha increased by 3- to more than 10-fold. TGF beta decreased the basal level and completely blocked the stimulatory action of ACTH on P-450(17) alpha enzyme activity. The effects of TGF beta on P-450(17) alpha enzyme content and mRNA levels were manifested in a dose-dependent manner, with maximal inhibition observed using 1 ng/ml TGF beta. Importantly, the inhibitory effects of TGF beta on P-450(17) alpha were not overcome by (Bu)2cAMP. These findings indicate that TGF beta is a potent negative regulator of P-450, and the inhibitory action appears to be at the level of P-450(17) alpha gene expression. The ability of TGF beta to suppress the positive stimulatory action of ACTH suggests that TGF beta could play a role in determining the pathway of steroidogenesis and, thereby, the specific steroids secreted by adrenocortical cells.

Publication types

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

MeSH terms

  • 17-alpha-Hydroxyprogesterone
  • Adrenal Cortex / drug effects
  • Adrenal Cortex / enzymology*
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Blotting, Western
  • Bucladesine / pharmacology
  • Cells, Cultured
  • Corticosterone / biosynthesis
  • Cortodoxone / metabolism
  • DNA Probes
  • Gene Expression Regulation*
  • Hydrocortisone / biosynthesis
  • Hydroxyprogesterones / metabolism
  • Nucleic Acid Hybridization
  • Progesterone / metabolism
  • RNA, Messenger / metabolism
  • Sheep
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Steroid Hydroxylases / antagonists & inhibitors*
  • Transforming Growth Factors / pharmacology*


  • DNA Probes
  • Hydroxyprogesterones
  • RNA, Messenger
  • Progesterone
  • Bucladesine
  • 17-alpha-Hydroxyprogesterone
  • Transforming Growth Factors
  • Adrenocorticotropic Hormone
  • Steroid Hydroxylases
  • Steroid 17-alpha-Hydroxylase
  • Corticosterone
  • Cortodoxone
  • Hydrocortisone