The steroid 11β-hydroxylase (P450c11) enzyme is responsible for the conversion of 11-deoxycortisolto cortisol in the zona fasciculata of the adrenalcortex. Animal studies have suggested that this enzyme or a closely related isozyme is also responsible for the successive 11β- and 18-hydroxylationand 18-oxidation of deoxycorticosterone requiredfor aldosterone synthesis in the zona glomerulosa.There are two distinct 110-hydroxylase genes inman, CYP11B1 and CYP11B2, which are predictedto encode proteins with 93% amino acid identity. Weused a sensitive assay based on the polymerasechain reaction to analyze the expression of theCYP11B1 and B2 genes. Transcripts of CYP11B1were detected at high levels in surgical specimensof normal adrenals and also in an aldosterone-secreting adrenal tumor. Transcripts of CYP11B2 werefound at low levels in normal adrenals, but at a muchhigher level in the aldosterone-secreting tumor.CYP11B2 mRNA levels were increased in culturedzona glomerulosa cells by physiological levels ofangiotensin-ll. The entire coding regions of bothCYP11B1 and B2 cDNAs were cloned from the tumormRNA. Expression of these cDNAs in cultured COS-1 cells demonstrated that the CYP11B1 productcould only 11β-hydroxylate 11-deoxycortisol ordeoxycorticosterone, whereas the CYP11B2 productcould also 18-hydroxylate cortisol or corticosterone.A small amount of aldosterone was synthesizedfrom deoxycorticosterone only in cells expressingCYP11B2 cDNA. These data demonstrate that theproduct of CYP11B2 is required for the final steps inthe synthesis of aldosterone.
ASJC Scopus subject areas
- Molecular Biology