Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (Type 2) isozyme of 11β-hydroxysteroid dehydrogenase

Anil K. Agarwal, Fraser M. Rogerson, Tomoatsu Mune, Perrin C. White

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11β-Hydroxysteroid dehydrogenase (11βHSD) converts glucocorticoids to inactive products and is thus thought to confer specificity for aldosterone on the type I mineralocorticoid receptor in the kidney. Recent studies indicate the presence of at least two isozymes of 11βHSD. In vitro, the NAD+-dependent kidney (type 2) isozyme catalyzes 11β-dehydrogenase but not reductase reactions, whereas the NADP+-dependent liver (type 1) isozyme catalyzes both reactions. We have now characterized the human gene encoding kidney 11βHSD (HSD11K). A bacteriophage P1 clone was isolated after screening a human genomic library by hybridization with sheep HSD11K cDNA. The gene consists of 5 exons spread over 6 kb. The nucleotide binding domain lies in the first and the second exon, and the catalytic domain in the fourth exon. The 5′ flanking sequences and first exon are GC-rich (80%), suggesting that the gene may he transcriptionally regulated by factors that recognize GC-rich sequences. Fluorescence in situ hybridization of metaphase chromosomes with a positive P1 clone localized the gene to chromosome 16q22. In contrast, the HSD11L (liver isozyme) gene is located on chromosome 1 and contains 6 exons; the coding sequences of these genes are only 21% identical. HSD11K is expressed at high levels in the placenta and kidney of midgestation human fetuses and at lower levels in lung and testes. Different transcriptional start sites are utilized in kidney and placenta. These data should be applicable to genetic analysis of the syndrome of apparent mineralocorticoid excess, which may represent a deficiency of 11βHSD.

Original languageEnglish (US)
Pages (from-to)195-199
Number of pages5
Issue number1
StatePublished - Sep 1 1995


ASJC Scopus subject areas

  • Genetics

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