Corticosterone oxidative neutralization by 11-β hydroxysteroid dehydrogenases in kidney and colon of the domestic fowl

A. Katz*, R. Heiblum, R. Meidan, B. Robinzon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

In mammalian organs involved in sodium reabsorption, the 11-β hydroxysteroid dehydrogenases (11βHSDs) oxidize glucocorticoids (GC) from their 11-alcohol form to their 11-keto state and therefore prevent their binding to mineralocorticoid (MC) receptors (MR) and the development of a MC excess syndrome. In birds the information about 11βHSDs and GC metabolism in such organs is scarce. Herein, we report the expression and enzymatic activity of 11βHSDs in the kidney and colon of chickens. Both organs express 11βHSD2-like mRNA. With NAD+, microsomes from both tissues oxidized corticosterone (CS) into 11-dehydrocorticosterone (DHC) with Km of 200 and 20 nM and Vmax of 13 and 2 pmol/mg protein/min in the kidney and colon, respectively. Thiram, a specific 11βHSD2 inhibitor, suppressed this oxidation in kidney. The expression and action of the putative 11βHSD3 were also tested. The chicken colon, and to a greater extent the kidney, expressed 11βHSD3-like mRNA. Microsomal fractions from both tissues oxidized CS into DHC in the presence of NADP+ with Km of 150 and 4 nM and Vmax of 5 and 0.3 pmol/mg protein/min for the kidney and the colon, respectively. This oxidation was not affected when NADP+ conversion into NAD+ was inhibited by excess pyrophosphate or a phosphatase inhibitor cocktail. In microsomes of chicken's duodenum, where 11βHSD1-like mRNA expression is high, NADP+-dependent oxidation of CS into DHC has a low-affinity Km of 1130 nM. This study documented the expression and activity of two enzymes that convert CS into DHC, one is 11βHSD2-like and the other is similar to the putative mammalian 11βHSD3.

Original languageEnglish
Pages (from-to)814-820
Number of pages7
JournalGeneral and Comparative Endocrinology
Volume155
Issue number3
DOIs
StatePublished - 1 Feb 2008

Keywords

  • 11β-Hydroxysteroid dehydrogenase
  • Chicken
  • Glucocorticoids
  • Intestine
  • Kidney

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