Transforming growth factor beta 1 is a negative regulator of steroid 17 alpha-hydroxylase expression in bovine adrenocortical cells.
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.
Perrin
A
A
Laboratoire BRCE, INSERM U-244, Centre d'Etudes Nucléaires, Grenoble, France.
Pascal
O
O
Defaye
G
G
Feige
J J
JJ
Chambaz
E M
EM
D000302:Adrenal Cortex / Q000201:enzymology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015151:Immunoblotting; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013254:Steroid 17-alpha-Hydroxylase