The enzyme 11β-hydroxysteroid dehydrogenase type II (11βHSD2) has been shown to confer specificity on mineralocorticoid receptors (MR) by inactivating glucocorticoids. In the present study we examined the colocalization of 11βHSD2 and MR in various exocrine and secretory glands by immunostaining of serial mirror tissue sections with subsequent computerized image analysis. Both 11βHSD2 and MR proteins were expressed in the same cells in the distal convoluted tubules, Henle's loop, and collecting tubules of the kidney and the absorptive epithelia of duodenum, jejunum, ileum, colon, and excretory ducts of anal and esophageal glands. Significantly, 11βHSD2 and MR immunoreactivity also colocalized in the respiratory tract, in collecting ducts of the tracheal and bronchial glands, ciliated bronchial epithelial cells, and type II alveolar epithelial cells, suggesting important and unexpected roles for mineralocorticoids in the lung. In the skin, 11βHSD2 and MR were present only in excretory ducts of eccrine sweat glands, but not in sebaceous or apocrine glands. In eccrine glands, MR immunoreactivity was present in the basal cells of excretory ducts, while 11βHSD2 immunoreactivity was localized in the luminal cells. Neither 11βHSD2 nor MR proteins were expressed in the lacrimal gland, prostate, bile ducts, gall bladder, urinary bladder, urethra, or ureter. These results indicate that 11βHSD2 protein colocalizes with MR protein in the great majority of sodium-transporting epithelia involved in serous secretion and supports the proposal that 11βHSD2 is a pivotal determinant of mineralocorticoid receptor occupancy in man. Furthermore, our demonstration of colocalization in discrete areas of the lung suggests that mineralocorticoid agonists or antagonists, and/or inhibitors of 11βHSD2, may have unexpected applications in respiratory disease.
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