Analysis of the human gene encoding the kidney isozyme of 11β-hydroxysteroid dehydrogenase

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

11β-Hydroxysteroid dehydrogenase (11β-HSD) catalyzes the conversion of cortisol to cortisone. This activity may be deficient in the syndrome of apparent mineralocorticoid excess (AME). 11β-HSD L (Type I), isolated from liver, is widely expressed and utilizes NADP+ as a cofactor. The gene for 11β-HSD L was found to be normal in patients of AME. A second isoform, 11β-HSD K (Type II), isolated from kidney, is more tissue specific in expression and utilizes NAD+ as a cofactor. The cDNA clone encoding 11β-HSD K was isolated from sheep kidney. The cDNA is 1.8 kb in length and encodes a protein of 404 amino acid residues with a predicted Mr 43,953. The recombinant enzyme functions as an NAD+-dependent 11β-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD+-dependent isozyme of 17β-hydroxysteroid dehydrogenase. It is expressed at high levels in the kidney, placenta, adrenal and at lower levels in colon, stomach, heart and skin. The human 11β-HSD K gene consists of five 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 promoter for 11β-HSD K gene lacks a TATA box and has a high GC base content, suggesting that the gene may be transcriptionally regulated by factors that recognize GC-rich sequences. Fluorescent in situ hybridization of metaphase chromosomes with a positive bacteriophage P1 genomic 11β-HSD K clone localized the gene to chromosome 16q22. In contrast, the 11β-HSD L gene is located on chromosome 1 and contains 6 exons; the coding sequences of these genes are only 21% identical. Different transcriptional start sites are utilized in kidney and placenta.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume55
Issue number5-6
DOIs
StatePublished - 1995

Fingerprint

11-beta-Hydroxysteroid Dehydrogenases
Gene encoding
Isoenzymes
Kidney
Genes
Exons
Chromosomes
NAD
Mineralocorticoids
Placenta
Apparent Mineralocorticoid Excess Syndrome
Oxidoreductases
Complementary DNA
Clone Cells
Bacteriophage P1
GC Rich Sequence
Amino Acids
TATA Box
Bacteriophages
Chromosomes, Human, Pair 1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Analysis of the human gene encoding the kidney isozyme of 11β-hydroxysteroid dehydrogenase. / Agarwal, Anil K.; Rogerson, Fraser M.; Mune, Tomoatsu; White, Perrin C.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 55, No. 5-6, 1995, p. 473-479.

Research output: Contribution to journalArticle

@article{fa43d6b1541248d3899614bbacf9389e,
title = "Analysis of the human gene encoding the kidney isozyme of 11β-hydroxysteroid dehydrogenase",
abstract = "11β-Hydroxysteroid dehydrogenase (11β-HSD) catalyzes the conversion of cortisol to cortisone. This activity may be deficient in the syndrome of apparent mineralocorticoid excess (AME). 11β-HSD L (Type I), isolated from liver, is widely expressed and utilizes NADP+ as a cofactor. The gene for 11β-HSD L was found to be normal in patients of AME. A second isoform, 11β-HSD K (Type II), isolated from kidney, is more tissue specific in expression and utilizes NAD+ as a cofactor. The cDNA clone encoding 11β-HSD K was isolated from sheep kidney. The cDNA is 1.8 kb in length and encodes a protein of 404 amino acid residues with a predicted Mr 43,953. The recombinant enzyme functions as an NAD+-dependent 11β-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37{\%} identical in amino acid sequence to an NAD+-dependent isozyme of 17β-hydroxysteroid dehydrogenase. It is expressed at high levels in the kidney, placenta, adrenal and at lower levels in colon, stomach, heart and skin. The human 11β-HSD K gene consists of five 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 promoter for 11β-HSD K gene lacks a TATA box and has a high GC base content, suggesting that the gene may be transcriptionally regulated by factors that recognize GC-rich sequences. Fluorescent in situ hybridization of metaphase chromosomes with a positive bacteriophage P1 genomic 11β-HSD K clone localized the gene to chromosome 16q22. In contrast, the 11β-HSD L gene is located on chromosome 1 and contains 6 exons; the coding sequences of these genes are only 21{\%} identical. Different transcriptional start sites are utilized in kidney and placenta.",
author = "Agarwal, {Anil K.} and Rogerson, {Fraser M.} and Tomoatsu Mune and White, {Perrin C.}",
year = "1995",
doi = "10.1016/0960-0760(95)00196-4",
language = "English (US)",
volume = "55",
pages = "473--479",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",
number = "5-6",

}

TY - JOUR

T1 - Analysis of the human gene encoding the kidney isozyme of 11β-hydroxysteroid dehydrogenase

AU - Agarwal, Anil K.

AU - Rogerson, Fraser M.

AU - Mune, Tomoatsu

AU - White, Perrin C.

PY - 1995

Y1 - 1995

N2 - 11β-Hydroxysteroid dehydrogenase (11β-HSD) catalyzes the conversion of cortisol to cortisone. This activity may be deficient in the syndrome of apparent mineralocorticoid excess (AME). 11β-HSD L (Type I), isolated from liver, is widely expressed and utilizes NADP+ as a cofactor. The gene for 11β-HSD L was found to be normal in patients of AME. A second isoform, 11β-HSD K (Type II), isolated from kidney, is more tissue specific in expression and utilizes NAD+ as a cofactor. The cDNA clone encoding 11β-HSD K was isolated from sheep kidney. The cDNA is 1.8 kb in length and encodes a protein of 404 amino acid residues with a predicted Mr 43,953. The recombinant enzyme functions as an NAD+-dependent 11β-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD+-dependent isozyme of 17β-hydroxysteroid dehydrogenase. It is expressed at high levels in the kidney, placenta, adrenal and at lower levels in colon, stomach, heart and skin. The human 11β-HSD K gene consists of five 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 promoter for 11β-HSD K gene lacks a TATA box and has a high GC base content, suggesting that the gene may be transcriptionally regulated by factors that recognize GC-rich sequences. Fluorescent in situ hybridization of metaphase chromosomes with a positive bacteriophage P1 genomic 11β-HSD K clone localized the gene to chromosome 16q22. In contrast, the 11β-HSD L gene is located on chromosome 1 and contains 6 exons; the coding sequences of these genes are only 21% identical. Different transcriptional start sites are utilized in kidney and placenta.

AB - 11β-Hydroxysteroid dehydrogenase (11β-HSD) catalyzes the conversion of cortisol to cortisone. This activity may be deficient in the syndrome of apparent mineralocorticoid excess (AME). 11β-HSD L (Type I), isolated from liver, is widely expressed and utilizes NADP+ as a cofactor. The gene for 11β-HSD L was found to be normal in patients of AME. A second isoform, 11β-HSD K (Type II), isolated from kidney, is more tissue specific in expression and utilizes NAD+ as a cofactor. The cDNA clone encoding 11β-HSD K was isolated from sheep kidney. The cDNA is 1.8 kb in length and encodes a protein of 404 amino acid residues with a predicted Mr 43,953. The recombinant enzyme functions as an NAD+-dependent 11β-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD+-dependent isozyme of 17β-hydroxysteroid dehydrogenase. It is expressed at high levels in the kidney, placenta, adrenal and at lower levels in colon, stomach, heart and skin. The human 11β-HSD K gene consists of five 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 promoter for 11β-HSD K gene lacks a TATA box and has a high GC base content, suggesting that the gene may be transcriptionally regulated by factors that recognize GC-rich sequences. Fluorescent in situ hybridization of metaphase chromosomes with a positive bacteriophage P1 genomic 11β-HSD K clone localized the gene to chromosome 16q22. In contrast, the 11β-HSD L gene is located on chromosome 1 and contains 6 exons; the coding sequences of these genes are only 21% identical. Different transcriptional start sites are utilized in kidney and placenta.

UR - http://www.scopus.com/inward/record.url?scp=0029598448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029598448&partnerID=8YFLogxK

U2 - 10.1016/0960-0760(95)00196-4

DO - 10.1016/0960-0760(95)00196-4

M3 - Article

VL - 55

SP - 473

EP - 479

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 5-6

ER -