Localization of 11 beta-hydroxysteroid dehydrogenase type II in human epithelial tissues.

Abstract

The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) confers specificity on the renal mineralocorticoid receptor by inactivating glucocorticoids. Mutations in this gene give rise to the syndrome of apparent mineralocorticoid excess, a congenital condition characterized by sodium retention, severe hypertension, and often by growth retardation. It is not known whether 11 beta HSD2 or another enzyme confers specificity in nonrenal sodium transporting epithelia, such as those in the sweat gland, salivary gland, and gastrointestinal tract. We previously have used the HUH23 antibody to localize 11 beta HSD2 in the human kidney, vascular smooth muscle cells, and placenta. In the present study, we have examined a range of human epithelia for the presence of 11 beta HSD2. In the skin, staining was seen in eccrine sweat glands and arterioles, whereas weak HUH23 immunostaining was observed in the epidermis. Staining was absent from sebaceous glands and hair follicles. In the parotid gland, the 11 beta HSD2 enzyme was present in striated and excretory ducts, whereas in the submandibular gland, it was found in striated and interlobular ducts. Acini, adipocytes, and associated tumor tissue did not stain with the HUH23 antibody. In the gastrointestinal tract, HUH23 stained ileal enterocytes, colonic absorptive cells, and epithelial goblet cells, whereas the rectum contained areas of staining and nonstaining absorptive cells. Gastrointestinal structures, such as the lamina propria, Peyer's patch, and goblet cells within the crypts of Lieberkuhn did not stain with the antibody. This study demonstrates the presence of 11 beta HSD2 in nonrenal sodium-transporting epithelia and describes a range of tissues affected in the syndrome of apparent mineralocorticoid excess.

Association of Adrenal Steroids With Hypertension and the Metabolic Syndrome in Blacks

“…[45][46][47] It is possible, however, that the small increase in salivary cortisol in hypertensive subjects was attributable, at least in part, to a decreased conversion of cortisol to cortisone by salivary 11-␤-hydroxysteroid dehydrogenase 2. 48 Nevertheless, the small increases in salivary cortisol reflect exposure of target tissue to increased glucocorticoid activity. 24,26 However, circulating cortisol may not reflect its activity in target tissues.…”

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

“…Positive immunostaining for 11b-HSD-type2 is found in surface and crypt colonic epithelial cells (41), and in striated ducts of the salivary glands (39). In the skin, 11b-HSD-type2 is located only in eccrine sweat glands, whereas sebaceous or apocrine glands are devoid of this`gatekeeper enzyme' (45). In the placenta, 11b-HSD-type2 is located in the syncytial trophoblast cells (fetal origin) that protect the fetus from high maternal GC concentrations (4, 39, 46,47), whereas the human decidual cells, formed from endometrial stromal cells (maternal origin), express Figure 1 Redox equilibrium of corticosteroids catalyzed by human kidney 11b-HSD-type2 (A) and liver 11b-HSD-type1 (B).…”

“…Topical application of GC to the skin causes a vasoconstriction of arterioles (42). This effect is enhanced by addition of 11b-HSD inhibitors, suggesting an involvement of 11b-HSD in the regulation of vascular tone by the amplification of responses to vasoconstrictors (44,45,99,100).…”

11β-hydroxysteroid dehydrogenase type II: a Potential target for prevention of colonic tumorigenesis

“…11ßHSD2 activity is higher in the colon than in the small intestine in the rat and it is primarily localized to intestinal epithelia [36]. In intestinal tumors, 11ßHSD2 is expressed in epithelial and stromal cells [37][38][39].…”