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Division of Pediatric Endocrinology, Cornell University Medical College New York, New York 10021
Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center Duarte, California 91010
Address requests for reprints to: Dr. Perrin C. White, Cornell University Medical College, Box 42, 1300 York Avenue, New York, New York 10021.
Abstract
The steroid 11β-hydroxylase (P450c11) enzyme is responsible for the conversion of 11-deoxycortisol 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.
FOOTNOTES
This work was supported by NIH Grants DK-37867 and DK- 42169 (to P.C.W.), DK-39721, and HL-44404 (to J.L.N.) and a grant from the Horace Goldsmith Foundation (to P.C.W.).
* Supported by a fellowship from the Kiosk Foundation.
Supported by a Fellowship for Graduate Studies in Health Sciences from the Consejo Nacional de Ciencia y Tecnologia (Mexico).
Irma T. Hirschl Trust Scholar.
Received for publication May 30, 1991. Revision received July 19, 1991. Accepted for publication July 19, 1991.
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