Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11{beta}-hydroxysteroid dehydrogenase

Journal Article · Fri Sep 01 00:00:00 EDT 1995 · Genomics

DOI:https://doi.org/10.1006/geno.1995.1231· OSTI ID:433301

Agarwal, A K; Rogerson, F M; Mune, T; White, P C ^[1]

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1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

11{beta}-hydroxysteroid dehydrogenase (11{beta}HSD) 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 11{beta}HSD. In vitro, the NAD{sup +}-dependent kidney (type 2) isozyme catalyzes 11{beta}-dehydrogenase but not reductase reactions, whereas the NADP{sup +}-dependent liver (type 1) isozyme catalyzes both reactions. We have now characterized the human gene encoding kidney 11{beta}HSD (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 exon are GC-rich (80%), suggesting that the gene may be 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 11{beta}HSD. 25 refs., 5 figs.

• OSTI ID: 433301
• Journal Information: Genomics, Vol. 29, Issue 1; Other Information: PBD: 1 Sep 1995
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
HUMAN CHROMOSOME 16
GENETIC MAPPING
OXIDOREDUCTASES
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION
TISSUE DISTRIBUTION
GENE REGULATION
MINERALOCORTICOIDS
RECEPTORS
GENES
DNA SEQUENCING
KIDNEYS
GLUCOCORTICOIDS
ALDOSTERONE
DNA HYBRIDIZATION
BACTERIOPHAGES
EXONS
NUCLEOTIDES
METABOLIC DISEASES
MAN
HYPERTENSION
HEREDITARY DISEASES