Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans.

Abstract:

:A gene encoding steroid 18-hydroxylase (P-450C18) was isolated from a human genomic DNA library. It was identified as CYP11B2, which was previously postulated to be a pseudogene or a less active gene closely related to CYP11B1, the gene encoding steroid 11 beta-hydroxylase (P-45011 beta) [Mornet, E., Dupont, J., Vitek, A. & White, P. C. (1989) J. Biol. Chem. 264, 20961-20967]. The nucleotide sequence of the promoter region of the P-450C18 gene is strikingly different from that of the P-45011 beta gene, although the sequences of their exons are 93% identical. The transient expression in Y-1 adrenal tumor cells of CAT constructs with a series of deletion mutants of promoter regions of both genes indicated that the two genes are regulated differently. P-450C18 as expressed in COS-7 cells exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta-hydroxylase activity as well. In contrast, P-45011 beta as expressed in the cultured cells exhibits steroid 11 beta-hydroxylase activity exclusively but fails to catalyze the synthesis of aldosterone and 18-oxocortisol. These results indicate that P-45011 beta and P-450C18 are products of two different genes and that the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.

authors

Kawamoto T,Mitsuuchi Y,Toda K,Yokoyama Y,Miyahara K,Miura S,Ohnishi T,Ichikawa Y,Nakao K,Imura H

doi

10.1073/pnas.89.4.1458

subject

Has Abstract,Author List Incomplete

pub_date

1992-02-15 00:00:00

pages

1458-62

issue

4

eissn

0027-8424

issn

1091-6490

journal_volume

89

pub_type

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