Transforming growth factor-β inhibits steroid 17α-hydroxylase cytochrome p-450 expression in ovine adrenocortical cells

W. E. Rainey, D. Naville, J. M. Saez, B. R. Carr, W. Byrd, R. R. Magness, J. I. Mason

Research output: Contribution to journalArticle

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Abstract

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, 17α-hydroxylase cytochrome P-450 (P-45017α) is a key enzyme controlling the formation of cortisol and androgens. Recently, we demonstrated that transforming growth factor-β (TGFβ) is a potent inhibitor of steroid production in ovine adrenocortical cells. In the present study we used a polyclonal antibody to P45017α to determine adrenal cell P-45017α enzyme content by Western analysis. In addition, we used a cDNA probe encoding for bovine P-45017α mRNA to determine levels of P-45017α 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-45017α activity, enzyme content, and mRNA levels for P-45017α increased by 3- to more than 10-fold. TGFβ decreased the basal level and completely blocked the stimulatory action of ACTH on P-45017α enzyme activity. The effects of TGFβ on P-45017α enzyme content and mRNA levels were manifested in a dose-dependent manner, with maximal inhibition observed using 1 ng/ml TGFβ. Importantly, the inhibitory effects of TGFβ on P-450i7a were not overcome by (Bu)2cAMP. These findings indicate that TGFβ is a potent negative regulator of P-450, and the inhibitory action appears to be at the level of P-45017α gene expression. The ability of TGFβ to suppress the positive stimulatory action of ACTH suggests that TGFβ could play a role in determining the pathway of steroidogenesis and, thereby, the specific steroids secreted by adrenocortical cells.

Original languageEnglish (US)
Pages (from-to)1910-1915
Number of pages6
JournalEndocrinology
Volume127
Issue number4
DOIs
StatePublished - Oct 1990

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ASJC Scopus subject areas

  • Endocrinology

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