Transforming growth factor beta 1 is a negative regulator of steroid 17 alpha-hydroxylase expression in bovine adrenocortical cells

Endocrinology. 1991 Jan;128(1):357-62. doi: 10.1210/endo-128-1-357.

Abstract

Transforming growth factor beta 1 (TGF-beta 1) has been shown previously to induce striking alterations of bovine adrenocortical cell steroidogenic functions. One of the major lesions was characterized as a loss of steroid-17 alpha-hydroxylase activity, a key step in the biosynthetic pathway leading to active corticosteroid hormones. The mechanism of this negative effect of TGF-beta 1 on adrenocortical differentiated functions was investigated. It was observed that: 1) bovine adrenocortical 17 alpha-hydroxylase activity rapidly decreased in cells exposed to TGF-beta 1, in a time (10-20 h)-dependent manner; 2) immunoblotting of the corresponding cytochrome P-450(17) alpha showed that the loss of activity was superimposable to the decrease of the cellular protein content; 3) the cell content in 17 alpha-hydroxylase messenger RNA sharply dropped under TGF-beta 1 treatment (70-75% loss within 3-4 h) as determined by Northern blot analysis; 4) TGF-beta 1 inhibited as well the induction of P-450(17) alpha normally observed under adrenocorticotropin treatment; and 5) these TGF-beta 1 effects were selectively directed toward P-450(17) alpha expression, whereas another major steroidogenic cytochrome, i.e. P-450scc, was not affected. These observations showed that TGF-beta 1 is a potent negative modulator of 17 alpha-hydroxylase expression in bovine adrenocortical cells, very possibly at the transcriptional level. TGF-beta 1 (whose gene is expressed in these cells) may thus be examined as a possible autocrine inhibitory factor implied in the regulation of adrenocortical differentiated functions, in balance with ACTH, which represents the major positive signal in this system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / enzymology*
  • Animals
  • Cattle
  • Cells, Cultured
  • Immunoblotting
  • Kinetics
  • Microsomes / enzymology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / isolation & purification
  • Steroid 17-alpha-Hydroxylase / metabolism*
  • Transforming Growth Factor beta / pharmacology*

Substances

  • RNA, Messenger
  • Transforming Growth Factor beta
  • Steroid 17-alpha-Hydroxylase