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-45017α 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
StatePublished - Oct 1990

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Steroid 17-alpha-Hydroxylase
Transforming Growth Factors
Cytochrome P-450 Enzyme System
Sheep
Adrenocorticotropic Hormone
Enzymes
Messenger RNA
Steroids
Primary Cell Culture
Serum-Free Culture Media
Mixed Function Oxygenases
Androgens
Hydrocortisone
Cultured Cells
Complementary DNA
Maintenance
Gene Expression
Antibodies

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Rainey, W. E., Naville, D., Saez, J. M., Carr, B. R., Byrd, W., Magness, R. R., & Mason, J. I. (1990). Transforming growth factor-β inhibits steroid 17α-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells. Endocrinology, 127(4), 1910-1915.

Transforming growth factor-β inhibits steroid 17α-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells. / Rainey, W. E.; Naville, D.; Saez, J. M.; Carr, B. R.; Byrd, W.; Magness, R. R.; Mason, J. I.

In: Endocrinology, Vol. 127, No. 4, 10.1990, p. 1910-1915.

Research output: Contribution to journalArticle

Rainey, WE, Naville, D, Saez, JM, Carr, BR, Byrd, W, Magness, RR & Mason, JI 1990, 'Transforming growth factor-β inhibits steroid 17α-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells', Endocrinology, vol. 127, no. 4, pp. 1910-1915.
Rainey, W. E. ; Naville, D. ; Saez, J. M. ; Carr, B. R. ; Byrd, W. ; Magness, R. R. ; Mason, J. I. / Transforming growth factor-β inhibits steroid 17α-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells. In: Endocrinology. 1990 ; Vol. 127, No. 4. pp. 1910-1915.
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