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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 11 3859-3863
Copyright © 1997 by The Endocrine Society

Original Studies

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

Gen Hirasawa, Hironobu Sasano, Ken-ichi Takahashi, Kouhei Fukushima, Takashi Suzuki, Nobuo Hiwatashi, Takayosi Toyota, Zygmunt S. Krozowski and Hiroshi Nagura

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.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
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.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
THE ENZYME 11ß-hydroxysteroid dehydrogenase type II (11ßHSD2) is thought to confer specificity on the nonselective mineralocorticoid receptor (MR) (1) by converting glucocorticoids to their receptor inactive metabolites, thereby allowing the much lower circulating level of aldosterone to bind to mineralocorticoid receptors (2, 3). When 11ßHSD2 is compromised, patients manifest severe hypertension, marked sodium retention, and hypokalemia (4, 5). Recent studies prove that selective aldosterone action requires the colocalization of MR and the enzyme 11ßHSD2 in target cells (6, 7, 8, 9).

In man, immunolocalization of MR has been reported in classic mineralocorticoid target tissues including kidney, pancreas, salivary and sweat glands, and gastrointestinal tracts (10, 11, 12, 13, 14), and that of 11ßHSD2 in kidney, gastrointestinal tracts, sweat, and salivary glands (15, 16, 17, 18, 19). To better understand mineralocorticoid action, it is important to determine whether MR and 11ßHSD2 proteins are expressed in the same cells or not. However, detailed intraglandular localization of 11ßHSD2 and MR, in particular colocalization, has not been established in man or other species. Therefore, in this study, we examined immunolocalization of MR and 11ßHSD2 in the same cells or tissues of various human exocrine or secretory glands including sodium transporting systems by employing immunostaining of serial mirror tissue sections and subsequent computer assisted image analysis.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Antibody production and characterization

The generation and characterization of the HUH23 and MINREC4 have been described previously (11, 12, 14, 15, 17). HUH23 is an immunopurified polyclonal antibody raised in rabbits against a synthetic peptide corresponding to the last 16 amino acid residues of human 11ßHSD2. The polyclonal antibody MINREC4 was raised in rabbits against a synthetic fusion protein corresponding to 167 amino acids of the N-terminal region of the human renal mineralocorticoid receptor.

Tissue collection and preparation

Nonpathologic human tissues were obtained from autopsy files (choroid plexus, bronchus, and trachea) and from surgical pathology files (other specimens) of The Tohoku University Hospital, Sendai, Japan. Histological examinations of these specimens revealed no significant pathologic abnormalities. Two serial 3 µm tissue sections were prepared and mounted on clean glue-coated glass slides, with the cut surfaces serving as mirror images, in order to examine expression of the enzyme and receptor in the same cell.

Immunostaining

Details of immunostaining were reported previously by the authors (11, 12). A pair of mirror image section were individually treated with the HUH23 antibody and MINREC4 for 18 h at 4C in a moist chamber (optimal dilutions; HUH23 antibody 1:70 and MINREC4 1:600, both diluted with 0.01 M PBS). The Biotin-Strept Avidin immunostaining system using the Histofine kit (Nichirei Co, Tokyo, Japan) was used. The specificity of immunohistochemical staining was confirmed by replacing the primary antibodies with preimmune rabbit serum or normal rabbit immunoglobulin G (IgG). No specific immunoreactivity was detected in such sections.

Computer image analysis

The images were directly captured through a digital CCD camera (ProgRes 3012 PPC, Krontron Electronik Co., Encring, Germany) with a PRI-Macintosh interface board attached to an operating light microscope. Resolution was set at 998x774 pixel. The images were subsequently transferred to a Power Macintosh 9500/120 personal computer-controlled operating system and processed with Macintosh software Adobe Photoshop 3.0J.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Results are summarized in Table 1Go. 11ßHSD2 immunoreactivity was present in the cytoplasm, while MR immunoreactivity was detected predominantly in the cytoplasm with some nuclear staining. MR and 11ßHSD2 immunoreactivity was focally detected in the smooth muscle cells of arteries and veins in these tissues. In kidney, both MR and 11ßHSD2 immunoreactivity were present in the same cells of distal convoluted tubules, thin and thick branches of Henle’s loop, and collecting tubules. MR and 11ßHSD2 proteins were not expressed in glomerulus and proximal convoluted tubules. In colon, both MR and 11ßHSD2 proteins were expressed in the same absorptive epithelial cells. In duodenum, jejunum, and ileum, focal immunoreactivity of both MR and 11ßHSD2 were detected in superficial epithelial columnar cells.


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  		Table 1. Summary of results

 
In salivary glands including submandibular and parotid glands, 11ßHSD2 and MR immunoreactivity was detected in striated ducts (Fig. 1Go, A and B). MR immunoreactivity was detected in some of these ductal cells in which 11ßHSD2 immunoreactivity was not observed. In stomach, MR and 11ßHSD2 were not present in columnar epithelial cells, but focal immunoreactivity of MR and 11ßHSD2 was detected in the gastric nongoblet epithelial cells undergoing intestinal metaplasia. In both esophagus and anus, neither MR nor 11ßHSD2 immunoreactivity was present in the squamous epithelia, but both were expressed in the same excretory ductal cells of both submucosal esophageal and anal glands. In the pancreas, the same cells of small ducts connecting acinar cells with intercalated ducts were immunohistochemically positive for both enzyme and MR, although some ductal cells expressed only MR immunoreactivity, as in the salivary gland.



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  		Figure 1. Immunohistochemical localization of 11ßHSD2 (A) and MR (B) in submandibular glands. Immunoreactivity was detected in striated ductal cells (x200, methyl green as nuclear stain).

 
In the respiratory tract, 11ßHSD2 and MR colocalized in collecting ducts of bronchial and tracheal submucosal glands (Fig. 2Go, A and B), whereas acinar cells of these glands were immunohistochemically negative for 11ßHSD2 and MR. Ciliated ductal cells of these glands demonstrated relatively weak MR immunoreactivity but were immunohistochemically negative for 11ßHSD2 (Fig. 2Go, A and B). Bronchial ciliated epithelial cells also demonstrated MR and 11ßHSD2 immunoreactivity, especially those in small bronchi without submucosal glands and cartilage (Fig. 3Go, A and B). In alveoli, type II alveolar epithelial cells showed both MR and 11ßHSD2 immunoreactivity.



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  		Figure 2. Immunohistochemical localization of 11ßHSD2 (A) and MR (B) in collecting duct of submucosal bronchial glands. Marked immunoreactivity was detected in collecting duct cells. Sporadic immunoreactivity of MR was also detected in ciliated bronchial epithelial cells (x200, methyl green as nuclear stain).

 


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  		Figure 3. Immunohistochemical localization of 11ßHSD2 (A) and MR (B) in ciliated bronchial epithelial cells. Both 11ßHSD2 and MR were expressed in these cells (x200, hematoxylin as nuclear stain).

 
In skin, both 11ßHSD2 and MR proteins were present in eccrine sweat glands, with neither expressed in apocrine or sebaceous glands. In eccrine sweat glands, MR and 11ßHSD2 were immunolocalized in the excretory ducts, but to different cells, with MR immunoreactivity found in the basal cells of the duct and 11ßHSD2 immunoreactivity in the luminal cells (Fig. 4Go, A and B). Neither MR nor 11ßHSD2 proteins were expressed in lacrimal gland, prostate, bile duct, gall bladder, urinary bladder, urethra, or ureter.



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  		Figure 4. Immunohistochemical localization of 11ßHSD2 (A) and MR (B) in eccrine sweat glands. 11ßHSD2 immunoreactivity was detected in the luminal cells of the excretory ducts, while MR immunoreactivity was detected in the basal cells (x400, methyl green as nuclear stain).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this study we have established the cellular localization of both MR and 11ßHSD2 proteins in tissues involved in ion and/or water transport including classical and nonclassical mineralocorticoid target tissues. Both 11ßHSD2 and MR are expressed in the same cells, with few exceptions, in a wide variety of exocrine cells in man. These findings confirm the importance of 11ßHSD2 in regulating systemic mineralocorticoid action in man. Immunolocalization of MR and 11ßHSD2 in kidney and in the gastrointestinal tract is consistent with previous findings (11, 12, 13, 15, 16, 18). Immunolocalization of MR and 11ßHSD2 in salivary glands and pancreas has also been previously reported (11, 15), and the results of our present study are generally consistent with these findings. MR and 11ßHSD2 have not been reported in excretory ducts of the submucosal glands of the anus and esophagus, but as in salivary glands and pancreas, aldosterone may act on these cells and modify serous secretory products.

An important observation in our present study was the presence of MR and 11ßHSD2 immunoreactivity in ciliated epithelial cells of the bronchus and type II alveolar epithelial cells. The presence of MR and 11ßHSD2 has not been directly demonstrated in the respiratory system except for in situ hybridization in fetal rat lung (20). However, Pagé et al. demonstrated 11ßHSD2 activity in human lung cells (21), and Krozowski and Funder previously reported the presence of mineralocorticoid receptor in the rat lung (22). It is well-known that a significant fraction of the osmotically driven water transport in the lung across alveolar and airway epithelium involves transcellular movement facilitated by plasma membrane water channels (23). In addition, the basal rates of sodium and fluid transport in alveoli depend on sodium uptake by channels on the apical membrane of alveolar type II cells followed by extrusion of sodium on the basolateral surface by Na K-ATPase (23). Cullen and Welsh also reported that Na+ absorption is both acutely and chronically regulated by mineralocorticoids in the canine tracheal epithelium (24). These findings, together with our present immunolocalization of MR and 11ßHSD2 in human respiratory tract, suggest that aldosterone also plays important roles in sodium transportation across alveolar, bronchial, and tracheal epithelium. In addition to these epithelia, MR and 11ßHSD2 are expressed in the collecting duct of submucosal glands in trachea and bronchus. Secretion from these submucosal glands contributes to maintaining a mucous layer over the entire surface of the respiratory tract. A mixture of serous and mucous secretions from these glands regulates the viscosity of secretion, such as sputum. Therefore, aldosterone can also contribute to regulation of viscosity in the respiratory tract through its actions on collecting ductal cells. The present study thus paves the way for further important investigations to examine the involvement of aldosterone in various pathological conditions of the human respiratory tract, including bronchial asthma, pulmonary edema, and others.

In the skin, both MR and 11ßHSD2 proteins are present in eccrine sweat glands, but not in the sebaceous and apocrine sweat glands. This finding suggests that aldosterone may modulate perspiration through eccrine sweat glands (15, 19). MR and 11ßHSD2 proteins are generally colocalized in the same cells, although some ductal cells expressed MR but not 11ßHSD2 immunoreactivity in the salivary glands, pancreas, and bronchial and tracheal submucosal glands. However, distinctive dissociation of MR and 11ßHSD2 expression was detected in the excretory ductal cells of eccrine sweat glands, i.e. MR was immunolocalized in the basal cells of the duct, while 11ßHSD2 immunoreactivity was found in the luminal cells. Little is known about aldosterone modulation of sweat gland secretion in the human skin, and further investigations are required to clarify the significance of the differential immunolocalization of MR and 11ßHSD2. MR and 11ßHSD2 were not present in the tissues primarily involved in mucous secretion including apocrine glands, sebaceous glands, prostate, and others. We could not detect MR and 11ßHSD2 in human prostate, but Pagé et al. demonstrated the presence of functional MR and 11ßHSD2 activity in human prostate cancer cell line LNCaP (25). It awaits further investigations to clarify these differences. Aldosterone may therefore be considered to be involved in modulating systemic serous but not mucous secretion and/or ion transport in man.

Received May 6, 1997.

Revised July 28, 1997.

Accepted July 29, 1997.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Krozowski ZS, Funder JW. 1983 Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity. Proc Nat Acad Sci USA. 80:6056–6060.[Abstract/Free Full Text]
  2. Edwards CR, Stewart PM, Burt D, et al. 1988 Localization of 11 beta-hydroxysteroid dehydrogenase—tissue specific protector of the mineralocorticoid receptor. Lancet. 2(8618):986–989.
  3. Funder JW, Pearce PT, Smith R, Smith AI. 1988 Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science. 242:583–585.[Abstract/Free Full Text]
  4. Stewart PM, Krozowski ZS, Gupta A, et al. 1996 Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11 beta-hydroxysteorid dehydrogenase type 2 gene. Lancet. 347:88–91.[CrossRef][Medline]
  5. Wilson RC, Krozowski ZS, Li K, et al. 1995 A mutation in the HSD11ß2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 80:2263–2266.[Abstract]
  6. Shimojo M, Ricketts ML, Petrelli MD, et al. 1997 Immunodetection of 11-beta hydroxysteroiddehydrogenase type 2 in human mineralocorticoid target tissues—evidence for nuclear localization. Endocrinology. 138:1305–1311.[Abstract/Free Full Text]
  7. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS. 1994 Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol. 105:R11–R17.
  8. Pacha J, Miksik I. 1994 Distribution of 11beta-hydroxysteroid dehydrogenase along the rat intestine. LifeSci. 54:745–749.
  9. Lombes M, Farman N, Oblin ME, et al. 1990 Immunohistochemicallocalization of renal mineralocorticoid receptor by using ananti-idiortypic antibody that is an internal image of aldosterone. Proc Nat Acad Sci USA. 87:1086–1088.[Abstract/Free Full Text]
  10. Mirshahi M, Pagano M, Razaghi A, Lazar G, Agarwal MK. 1992 Immunophotochemical analysis of mineralocorticoidreceptor by polyclonal antibodies against the native receptor from rat kidney. Biochem Med Metab Biol. 47:133–144.[CrossRef][Medline]
  11. Sasano H, Fukushima K, Sasaki I, Matsuno S, Nagura H, Krozowski ZS. 1992 Immunolocalization of mineralocorticoid receptor in human kidney, pancreas, salivary, mammary, and sweat glands: a light and electron microscopic immunohistochemical study. J Endocrinol. 132:305–310.[Abstract]
  12. Fukushima K, Sasano H, Nagura H, Sasaki I, Matsuno S, Krozowski ZS. 1991 Immunohistochemical localization of mineralocorticoid receptor in human gut. Tohoku J Exp Med. 165:155–163.[Medline]
  13. Rundle SE, Smith AI, Stockman D, Funder JW. 1989 Immunocytochemical demonstration of mineralocorticoid receptors in rat and human kidney. J Ster Biochem. 33:1235–1242.[CrossRef][Medline]
  14. Krozowski ZS, Rundle SE, Wallace C, et al. 1989 Immunolocalization of renal mineralocorticoid receptors with an antiserum against a peptide deduced from the complementary deoxyribonucleic acid sequence. Endocrinology. 125:192–198.[Abstract]
  15. Smith RE, Maguire JA, Stein-Oakley AN, et al. 1996 Localization of 11 beta-hydroxysteroid dehydrogenase type II in human epithelial tissues. J Clin Endocrinol Metab. 81:3244–3248.[Abstract]
  16. Kyossev Z, Walker PD, Reeves WB. 1996 Immunolocalization of NAD-dependent 11 beta-hydroxysteroid dehydrogenase in human kidney and colon. Kidney Int. 49:271–281.[Medline]
  17. Krozowski Z, MaGuire JA, Stein-Oakley AN, Dowling J, Smith RE, Andrews RK. 1995 Immunohistochemical localization of the 11 beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta. J Clin Endocrinol Metab. 80:2203–2209.[Abstract]
  18. Whorwood CB, Ricketts ML, Stewart PM. 1994 Epithelial cell localization of type 2 11 beta-hydroxysteroid dehydrogenase in rat and human colon. Endocrinology. 135:2533–2541.[Abstract]
  19. Kenouch S, Lombes M, Delahaye F, Eugene E, Bonvalet JP, Farman N. 1994 Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab. 79:1334–1341.[Abstract]
  20. Brown RW, Diaz R, Robson AC, et al. 1996 The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology. 137:794–797.[Abstract]
  21. Pagé N, Warriar N, Govindan MV. 1994 11 beta-hydroxysteroid dehydrogenase activity in human lung cells and transcription regulation by glucocorticoids. Am J Physiol. 267:L464–L474.
  22. Krozowski Z, Funder JW. 1981 Mineralocorticoid receptors in the rat lung. Endocrinology. 109:1811–1813.[Abstract]
  23. Matthay MA, Folkesson HG, Verkman AS. 1996 Salt and water transport across alveolar and distal airway epithelia in the adult lung. Am J Physiol. 270:L487–503.
  24. Cullen JJ, Welsh MJ. 1987 Regulation of sodium absorption by canine tracheal epithelium. J Clin Invest. 79:73–79.
  25. Pagé N, Warriar N, Govindan MV. 1994 11ß-hydroxysterlid dehydrogenase and tissue specificity of androgen action in human prostate cancer cell LNCaP. J Steroid Biochem Molec Biol. 49:173–181.[CrossRef][Medline]



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