This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirasawa, G. Articles by Nagura, H. Search for Related Content PubMed PubMed Citation Articles by Hirasawa, G. Articles by Nagura, H.

Colocalization of 11ß-Hydroxysteroid Dehydrogenase Type II and Mineralocorticoid Receptor in Human Epithelia

Departments of Pathology (G.H., H.S., K-I.T., T.S., H.N.), Medicine (G.H., N.H., T.T.), and Surgery (K.F.), Tohoku University School of Medicine, Sendai, Japan; Laboratory of Molecular Hypertension (Z.S.K.), Baker Medical Research Institute, Prahran, Australia

Address correspondence and requests for reprints to: Hironobu Sasano, M.D., Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryou-machi, Sendai, Japan 980.

The enzyme 11ß-hydroxysteroid dehydrogenase type II (11ßHSD2) has been shown to confer specificity on mineralocorticoid receptors (MR) by inactivating glucocorticoids. In the present study we examined the colocalization of 11ßHSD2 and MR in various exocrine and secretory glands by immunostaining of serial mirror tissue sections with subsequent computerized image analysis. Both 11ßHSD2 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, 11ßHSD2 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, 11ßHSD2 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 11ßHSD2 immunoreactivity was localized in the luminal cells. Neither 11ßHSD2 nor MR proteins were expressed in the lacrimal gland, prostate, bile ducts, gall bladder, urinary bladder, urethra, or ureter. These results indicate that 11ßHSD2 protein colocalizes with MR protein in the great majority of sodium-transporting epithelia involved in serous secretion and supports the proposal that 11ßHSD2 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 11ßHSD2, may have unexpected applications in respiratory disease.

This article has been cited by other articles:

				J. Kim, K. A. Temple, S. A. Jones, K. N. Meredith, J. L. Basko, and M. J. Brady Differential Modulation of 3T3-L1 Adipogenesis Mediated by 11beta-Hydroxysteroid Dehydrogenase-1 Levels J. Biol. Chem., April 13, 2007; 282(15): 11038 - 11046. [Abstract] [Full Text] [PDF]

				A. Naray-Fejes-Toth and G. Fejes-Toth Novel mouse strain with Cre recombinase in 11beta-hydroxysteroid dehydrogenase-2-expressing cells Am J Physiol Renal Physiol, January 1, 2007; 292(1): F486 - F494. [Abstract] [Full Text] [PDF]

				P. Agostoni, A. Magini, D. Andreini, M. Contini, A. Apostolo, M. Bussotti, G. Cattadori, and P. Palermo Spironolactone improves lung diffusion in chronic heart failure Eur. Heart J., January 2, 2005; 26(2): 159 - 164. [Abstract] [Full Text] [PDF]

				J. R. Seckl, N. M. Morton, K. E. Chapman, and B. R. Walker Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue Recent Prog. Horm. Res., January 1, 2004; 59(1): 359 - 393. [Abstract] [Full Text]

				R. Norregaard, T. R. Uhrenholt, C. Bistrup, O. Skott, and B. L. Jensen Stimulation of 11-{beta}-hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake Am J Physiol Renal Physiol, August 1, 2003; 285(2): F348 - F358. [Abstract] [Full Text] [PDF]

				M. A. Miller, S. J. Kottler, J. A. Ramos-Vara, P. J. Johnson, V. K. Ganjam, and T. J. Evans 3-Methylindole Induces Transient Olfactory Mucosal Injuryin Ponies Vet. Pathol., July 1, 2003; 40(4): 363 - 370. [Abstract] [Full Text] [PDF]

				S. Diederich, E. Eigendorff, P. Burkhardt, M. Quinkler, C. Bumke-Vogt, M. Rochel, D. Seidelmann, P. Esperling, W. Oelkers, and V. Bahr 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2: An Important Pharmacokinetic Determinant for the Activity of Synthetic Mineralo- and Glucocorticoids J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5695 - 5701. [Abstract] [Full Text] [PDF]

				B. E. ORSIDA, Z. S. KROZOWSKI, and E. H. WALTERS Clinical Relevance of Airway 11beta -Hydroxysteroid Dehydrogenase Type II Enzyme in Asthma Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 1010 - 1014. [Abstract] [Full Text] [PDF]

				S. Kataoka, A. Kudo, H. Hirano, H. Kawakami, T. Kawano, E. Higashihara, H. Tanaka, F. Delarue, J.-D. Sraer, T. Mune, et al. 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Is Expressed in the Human Kidney Glomerulus J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 877 - 882. [Abstract] [Full Text] [PDF]

				K. E. Sheppard, S. Hourigan, K. X. Z. Li, and Z. S. Krozowski Novel nuclear corticosteroid binding in rat small intestinal epithelia Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G536 - G542. [Abstract] [Full Text] [PDF]

				R. Alzamora, L. Michea, and E. T. Marusic Role of 11{beta}-Hydroxysteroid Dehydrogenase in Nongenomic Aldosterone Effects in Human Arteries Hypertension, May 1, 2000; 35(5): 1099 - 1104. [Abstract] [Full Text] [PDF]

				G. Hirasawa, J. Takeyama, H. Sasano, K. Fukushima, T. Suzuki, Y. Muramatu, A. D. Darnel, C. Kaneko, N. Hiwatashi, T. Toyota, et al. 11{beta}-Hydroxysteroid Dehydrogenase Type II and Mineralocorticoid Receptor in Human Placenta J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1306 - 1309. [Abstract] [Full Text]

				K. Kato, H. Sasano, S. Ohara, H. Sekine, S. Mochizuki, T. Mune, K. Yasuda, H. Nagura, T. Shimosegawa, T. Toyota, et al. Coexpression of Mineralocorticoid Receptors and 11{beta}-Hydroxysteroid Dehydrogenase 2 in Human Gastric Mucosa J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2568 - 2573. [Abstract] [Full Text]

				G. Hirasawa, H. Sasano, T. Suzuki, J. Takeyama, Y. Muramatu, K. Fukushima, N. Hiwatashi, T. Toyota, H. Nagura, and Z. S. Krozowski 11{beta}-Hydroxysteroid Dehydrogenase Type 2 and Mineralocorticoid Receptor in Human Fetal Development J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1453 - 1458. [Abstract] [Full Text]

				T. Suzuki, H. Sasano, S. Suzuki, G. Hirasawa, J. Takeyama, Y. Muramatsu, F. Date, H. Nagura, and Z. S. Krozowski 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in Human Lung: Possible Regulator of Mineralocorticoid Action J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 4022 - 4025. [Abstract] [Full Text]