title: Corticosterone oxidative neutralization by 11-beta hydroxysteroid dehydrogenases in kidney and colon of the domestic fowl.
abstract: In mammalian organs involved in sodium reabsorption, the 11-beta hydroxysteroid dehydrogenases (11betaHSDs) 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 11betaHSDs and GC metabolism in such organs is scarce. Herein, we report the expression and enzymatic activity of 11betaHSDs in the kidney and colon of chickens. Both organs express 11betaHSD2-like mRNA. With NAD(+), microsomes from both tissues oxidized corticosterone (CS) into 11-dehydrocorticosterone (DHC) with K(m) of 200 and 20nM and V(max) of 13 and 2pmol/mg protein/min in the kidney and colon, respectively. Thiram, a specific 11betaHSD2 inhibitor, suppressed this oxidation in kidney. The expression and action of the putative 11betaHSD3 were also tested. The chicken colon, and to a greater extent the kidney, expressed 11betaHSD3-like mRNA. Microsomal fractions from both tissues oxidized CS into DHC in the presence of NADP(+) with K(m) of 150 and 4nM and V(max) of 5 and 0.3pmol/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 11betaHSD1-like mRNA expression is high, NADP(+)-dependent oxidation of CS into DHC has a low-affinity K(m) of 1130nM. This study documented the expression and activity of two enzymes that convert CS into DHC, one is 11betaHSD2-like and the other is similar to the putative mammalian 11betaHSD3.
authors.affiliation: Department of Animal Sciences, The Faculty of Agricultural, Food and Environmental Quality Science, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel. amnonkatz@ucla.edu
authors.forename: A
authors.initials: A
authors.lastname: Katz
authors.forename: R
authors.initials: R
authors.lastname: Heiblum
authors.forename: R
authors.initials: R
authors.lastname: Meidan
authors.forename: B
authors.initials: B
authors.lastname: Robinzon
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011200:Poultry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone