Light and electron microscopy localization of the 11beta-hydroxysteroid dehydrogenase type I enzyme in the rat.
The 11beta-hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) converts cortisone to cortisol in humans, and 11-dehydrocorticosterone to corticosterone in rodents. In the present study we used a new immunopurified polyclonal antibody, RAH113, to localize 11betaHSD1 at the light and electron microscopy levels in a wide range of rat tissues. 11betaHSD1 staining in the liver was of highest intensity around the central vein and decreased radially. In the lung, 11betaHSD1 was found at highest levels in the interstitial fibroblast, with levels in the type II pneumocyte an order of magnitude lower. RAH113 stained proximal tubules of the renal cortex and interstitial cells of the medulla and papilla. Adrenal 11betaHSD1 was confined to the glomerulosa and medulla, whereas the glucocorticoid-inactivating hydroxysteroid dehydrogenase isoform 11betaHSD2 was present in fascilulata/reticularis. 11betaHSD1 was found in parietal cells of the fundic region of the stomach, but not in the antrum. In the heart, 11betaHSD1 was detected in cells resembling interstitial fibroblasts of the endocardium and in the adventitial fibroblasts of blood vessels. Western blot analysis confirmed the presence of an antigen of the correct size (34 kDa) and intensity consistent with levels of enzyme activity previously reported in these tissues. Brain and testis also displayed the 34-kDa protein, confirming the expression of authentic 11betaHSD1 in these tissues. Electron microscopy of lung and kidney interstitial cells showed that 11betaHSD1 was localized both to the endoplasmic reticulum and the nuclear membrane. These results show that 11betaHSD1 is present in discrete cell populations where it may facilitate intracrine and paracrine glucocorticoid action in addition to its classical role of maintaining circulating glucocorticoids via activity in the liver.
Laboratories of Molecular Hypertension, Baker Medical Research Institute, Melbourne, Victoria 8008, Australia.
P S
PS
Brereton
R R
RR
van Driel
Suhaimi Fb
K
K
Koyama
R
R
Dilley
Z
Z
Krozowski
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000818:Animals; D015153:Blotting, Western; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D019899:Paracrine Communication / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000201:enzymology; D014018:Tissue Distribution
D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2