Immunolocalization of NAD-dependent 11β-hydroxysteroid dehydrogenase in human kidney and colon

Zhetcho Kyossev, Patrick D. Walker, W. Brian Reeves

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

The inactivation of physiological glucocorticoids by 11β-hydroxysteroid dehydrogenase (11β-HSD) confers mineralocorticoid specificity to certain aldosterone target tissues. Both NADP, and NAD-dependent isoforms of 11β-HSD have been described. An NAD-dependent isoform of 11β-HSD (11β-HSD2) was recently cloned from human kidney. Tile present studies were designed to examine the cellular distribution of 11β-HSD2 in human kidney and colon, and to determine if the cellular distribution of 11β-HSD2 within the human kidney and colon is consistent with a role in conferring mineralocorticoid specificity. Using antibodies against a fusion protein containing a portion of the human 11β-HSD2, immunohistochemical staining of human kidney showed intense, specific staining, of connecting tubules and cortical and medullary collecting tubules and less intense staining in the cortical thick ascending limb. No immunoreactivity was found in proximal tubules, glomeruli, or blood vessels. Within the collecting tubules staining was heterogeneous. The majority of cells showed intense cytoplasmic staining while α-intercalated cells displayed much less immunoreactivity. Within the colon, 11β-HSD2 immunoreactivity was found predominantly in surface epithelial cells but not in submucosal tissues. Thus, the distribution of the cloned NAD-dependent 11β-HSD2 parallels the distribution of mineralocorticoid receptors within the kidney and colon. These results support the view that the NAD-dependent isoform of 11β-HSD (11β-HSD2) provides mineralocorticoid specificity by inactivating glucocorticoids in an autocrine fashion.

Original languageEnglish (US)
Pages (from-to)271-281
Number of pages11
JournalKidney international
Volume49
Issue number1
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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