Multiple patterns of 11 beta-hydroxysteroid dehydrogenase catalytic activity along the mammalian nephron.
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examined whether 11 beta-OHSD is similarly located along the nephron of other mammals. Various tubular segments were microdissected from the mouse, rat, and rabbit nephron, and incubated for two hours at 37 degrees C in the presence of 11 nM [3H]-corticosterone (B). Thereafter, the respective amounts of B and [3H]-11dehydrocorticosterone (A) in the incubation solution were measured by HPLC. In the rabbit, the mouse and the rat, about 520 pmol/10 mm of B were transformed into A in tubular segments possessing MR, that is, the distal parts of the nephron (distal and collecting tubule). Differences appeared in the aldosterone-insensitive proximal tubule; in both the initial and final parts of this segment, 11 beta-OHSD activity was low (26 pmol/10 mm) in the rabbit and the mouse, and relatively high in the rat (328 pmol/10 mm). In the cortical part of the loop of Henle, where the presence of MR is still under discussion, 11 beta-OHSD activity was low in the mouse (70 pmol/10 mm), high in the rat (533 pmol/10 mm) and intermediate in the rabbit (227 pmol/10 mm). The comparison of these results with previous data obtained with immunohistochemical methods suggests that the proximal and distal nephron might express different isoforms of 11 beta-OHSD.
Kenouch
S
S
INSERM U246, Faculté de Médecine X. Bichat, Paris, France.
Coutry
N
N
Farman
N
N
Bonvalet
J P
JP
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D003345:Corticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D051379:Mice; D009399:Nephrons / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism; D013045:Species Specificity; D014018:Tissue Distribution
D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D003345:Corticosterone