G. Hirasawa et al., COLOCALIZATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-II AND MINERALOCORTICOID RECEPTOR IN HUMAN EPITHELIA, The Journal of clinical endocrinology and metabolism, 82(11), 1997, pp. 3859-3863
The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2)
has been shown to confer specificity on mineralocorticoid receptors (
MR) by inactivating glucocorticoids. In the present study we examined
the colocalization of 11 beta HSD2 and MR in various exocrine and secr
etory glands by immunostaining of serial mirror tissue sections with s
ubsequent computerized image analysis. Both 11 beta HSD2 and MR protei
ns 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 a
nal and esophageal glands. Significantly, 11 beta HSD2 and MR immunore
activity also colocalized in the respiratory tract, in collecting duct
s 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, 11
beta HSD2 and MR were present only in excretory ducts of eccrine sweat
glands, but not in sebaceous or apocrine glands. In eccrine glands, M
R immunoreactivity was present in the basal cells of excretory ducts,
while 11 beta HSD2 immunoreactivity was localized in the luminal cells
. Neither 11 beta HSD2 nor MR proteins were expressed in the lacrimal
gland, prostate, bile ducts, gall bladder, urinary bladder, urethra, o
r meter. These results indicate that 11 beta HSD2 protein colocalizes
with MR protein in the great majority of sodium-transporting epithelia
involved in serous secretion and supports the proposal that 11 beta H
SD2 is a pivotal determinant of mineralocorticoid receptor occupancy i
n man. Furthermore, our demonstration of colocalization in discrete ar
eas of the lung suggests that mineralocorticoid agonists or antagonist
s, and/or inhibitors of 11 beta HSD2, may have unexpected applications
in respiratory disease.