Light and electron microscopy localization of the 11 ss-hydroxysteroid dehydrogenase type I enzyme in the rat

The 11 beta -hydroxysteroid dehydrogenase type I enzyme (11 beta HSD1) conv erts cortisone to cortisol in humans, and 11-dehydrocorticosterone to corti costerone in rodents. In the present study we used a new immunopurified pol yclonal antibody, RAH113, to localize 11 beta HSD1 at the light and electro n microscopy levels in a wide range of rat tissues. 11 beta HSD1 staining i n the liver was of highest intensity around the central vein and decreased radially. In the lung, 11 beta HSD1 was found at highest levels in the inte rstitial fibroblast, with levels in the type II pneumocyte an order of magn itude lower. RAH113 stained proximal tubules of the renal cortex and inters titial cells of the medulla and papilla. Adrenal 11 beta HSD1 was confined to the glomerulosa and medulla, whereas the glucocorticoid-inactivating hyd roxysteroid dehydrogenase isoform 11 beta HSD2 was present in fascilulata/r eticularis. 11 beta HSD1 was found in parietal cells of the fundic region o f the stomach, but not in the antrum. In the heart, 11 beta HSD1 was detect ed in cells resembling interstitial fibroblasts of the endocardium and in t he adventitial fibroblasts of blood vessels. Western blot analysis confirme d the presence of an antigen of the correct size (34 kDa) and intensity con sistent with levels of enzyme activity previously reported in these tissues . Brain and testis also displayed the 34-kDa protein, confirming the expres sion of authentic 11 beta HSD1 in these tissues. Electron microscopy of lun g and kidney interstitial cells showed that 11 beta HSD1 was localized both to the endoplasmic reticulum and the nuclear membrane. These results show that 11 beta HSD1 is present in discrete cell populations where it may faci litate intracrine and paracrine glucocorticoid action in addition to its cl assical role of maintaining circulating glucocorticoids via activity in the liver.