Immunolocalization of NAD-dependent 11 beta-hydroxysteroid dehydrogenase in human kidney and colon.
The inactivation of physiological glucocorticoids by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) confers mineralocorticoid specificity to certain aldosterone target tissues. Both NADP, and NAD-dependent isoforms of 11 beta-HSD have been described. An NAD-dependent isoform of 11 beta-HSD (11 beta-HSD2) was recently cloned from human kidney. The present studies were designed to examine the cellular distribution of 11 beta-HSD2 in human kidney and colon, and to determine if the cellular distribution of 11 beta-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 11 beta-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 alpha-intercalated cells displayed much less immunoreactivity. Within the colon, 11 beta-HSD2 immunoreactivity was found predominantly in surface epithelial cells but not in submucosal tissues. Thus, the distribution of the cloned NAD-dependent 11 beta-HSD2 parallels the distribution of mineralocorticoid receptors within the kidney and colon. These results support the view that the NAD-dependent isoform of 11 beta-HSD (11 beta-HSD2) provides mineralocorticoid specificity by inactivating glucocorticoids in an autocrine fashion.
Kyossev
Z
Z
Division of Nephrology, University of Arkansas for Medical Sciences, Little Rock, USA.
Walker
P D
PD
Reeves
W B
WB
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D011817:Rabbits; D014407:Tumor Cells, Cultured
D009243:NAD; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases