The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex

Kathleen M. Curnow, Maria Teresa Tusie-Luna, Leigh Pascoe, Rama Natarajan, Jia Li Gu, Jerry L. Nadler, Perrin C. White

Research output: Contribution to journalArticle

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Abstract

The steroid 11β-hydroxylase (P450c11) enzyme is responsible for the conversion of 11-deoxycortiso to cortisol in the zona fasciculata of the adrenal cortex. Animal studies have suggested that this enzyme or a closely related isozyme is also responsible for the successive 11β- and 18-hydroxylation and 18-oxidation of deoxycorticosterone required for aldosterone synthesis in the zona glomerulosa There are two distinct 11β-hydroxylase genes in man, CYP11B1 and CYP11B2, which are predicted to encode proteins with 93% amino acid identity. We used a sensitive assay based on the polymerase chain reaction to analyze the expression of the CYP11B1 and B2 genes. Transcripts of CYP11B1 were detected at high levels in surgical specimens of normal adrenals and also in an aldosterone-secreting adrenal tumor. Transcripts of CYP11B2 were found at low levels in normal adrenals, but at a much higher level in the aldosterone-secreting tumor CYP11B2 mRNA levels were increased in cultured zona glomerulosa cells by physiological levels of angiotensin-II. The entire coding regions of both CYP11B1 and B2 cDNAs were cloned from the tumor mRNA. Expression of these cDNAs in cultured COS-1 cells demonstrated that the CYP11B1 product could only 11β-hydroxylate 11-deoxycortisol or deoxycorticosterone, whereas the CYP11B2 product could also 18-hydroxylate cortisol or corticosterone. A small amount of aldosterone was synthesized from deoxycorticosterone only in cells expressing CYP11B2 cDNA. These data demonstrate that the product of CYP11B2 is required for the final steps in the synthesis of aldosterone.

Original languageEnglish (US)
Pages (from-to)1513-1522
Number of pages10
JournalMolecular Endocrinology
Volume5
Issue number10
StatePublished - 1991

Fingerprint

Steroid 11-beta-Hydroxylase
Cytochrome P-450 CYP11B2
Adrenal Cortex
Aldosterone
Desoxycorticosterone
Genes
Zona Glomerulosa
Complementary DNA
Hydrocortisone
Cortodoxone
Zona Fasciculata
Messenger RNA
Glandular and Epithelial Neoplasms
COS Cells
Enzymes
Hydroxylation
Corticosterone
Mixed Function Oxygenases
Angiotensin II
Isoenzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Curnow, K. M., Tusie-Luna, M. T., Pascoe, L., Natarajan, R., Gu, J. L., Nadler, J. L., & White, P. C. (1991). The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Molecular Endocrinology, 5(10), 1513-1522.

The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. / Curnow, Kathleen M.; Tusie-Luna, Maria Teresa; Pascoe, Leigh; Natarajan, Rama; Gu, Jia Li; Nadler, Jerry L.; White, Perrin C.

In: Molecular Endocrinology, Vol. 5, No. 10, 1991, p. 1513-1522.

Research output: Contribution to journalArticle

Curnow, KM, Tusie-Luna, MT, Pascoe, L, Natarajan, R, Gu, JL, Nadler, JL & White, PC 1991, 'The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex', Molecular Endocrinology, vol. 5, no. 10, pp. 1513-1522.
Curnow KM, Tusie-Luna MT, Pascoe L, Natarajan R, Gu JL, Nadler JL et al. The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Molecular Endocrinology. 1991;5(10):1513-1522.
Curnow, Kathleen M. ; Tusie-Luna, Maria Teresa ; Pascoe, Leigh ; Natarajan, Rama ; Gu, Jia Li ; Nadler, Jerry L. ; White, Perrin C. / The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. In: Molecular Endocrinology. 1991 ; Vol. 5, No. 10. pp. 1513-1522.
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