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 [H-3]-corticosterone (B). Thereafter, the respective amounts of B and [H-3]-11 dehydrocorticosterone (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.