help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Suzuki, T.
Right arrow Articles by Krozowski, Z. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, T.
Right arrow Articles by Krozowski, Z. S.
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 11 4022-4025
Copyright © 1998 by The Endocrine Society

Original Studies

11ß-Hydroxysteroid Dehydrogenase Type 2 in Human Lung: Possible Regulator of Mineralocorticoid Action

Takashi Suzuki, Hironobu Sasano, Satoshi Suzuki, Gen Hirasawa, Junji Takeyama, Yasunari Muramatsu, Fumiko Date, Hiroshi Nagura and Zygmunt S. Krozowski

Department of Pathology, Tohoku University School of Medicine (T.S., H.S., G.H., J.T., Y.M., F.D., H.N.), and the Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University (S.S.), Sendai 980-8575, Japan; and the Laboratory of Molecular Hypertension, Baker Medical Research Institute (Z.S.K.), Melbourne, Australia

Address all correspondence and requests for reprints to: Takashi Suzuki M.D., Department of Pathology, Tohoku University School of Medicine, 2–1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. E-mail: t-suzuki{at}patholo2.med.tohoku.ac.jp


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
11ß-Hydroxysteroid dehydrogenase type 2 (11ßHSD2) catalyzes the conversion of cortisol to biologically inactive cortisone and is thought to confer specificity on mineralocorticoid receptors (MR). Cortisol is a prerequisite for surfactant synthesis and fetal lung maturation. Recently, expression of 11ßHSD2 was demonstrated in human fetal lung, but its localization and possible biological roles remain unknown. Therefore, in this study, we examined immunohistochemical localization of 11ßHSD2, MR, and glucocorticoid receptor (GR) in nonpathological human lungs from fetus to adult (8 weeks gestation to 55 yr of age; n = 40) retrieved from pathology files. Both 11ßHSD2 and MR immunoreactivities were detected in airway epithelia, from bronchiole to trachea and in fetal and neonatal ciliated collecting duct cells of tracheal and bronchial glands, but were undetectable in alveoli. On the other hand, GR was detected in all cell types. These results indicate that 11ßHSD2 colocalizes with MR in human airway epithelia and suggest that 11ßHSD2 play an important role in pulmonary mineralocorticoid activity such as sodium and fluid transport.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
11ß-HYDROXYSTEROID dehydrogenase type 2 (11ßHSD2) catalyzes the conversion of bioactive glucocorticoid, cortisol, to the hormonally inactive 11-keto metabolite, cortisone, regulating the access of cortisol to glucocorticoid (GR) or mineralocorticoid (MR) receptor (1, 2, 3). 11ßHSD2 is highly expressed in the human placenta and various fetal tissues (1, 4, 5, 6), and is thought to protect the developing fetus from the high levels of maternal cortisol. 11ßHSD2 has also been reported in adult human mineralocorticoid target tissues, including kidney, pancreas, salivary glands, and colon (7, 8), where it confers mineralocorticoid specificity by protecting the nonselective MR from cortisol occupation (9, 10). Recently, Hirasawa et al. (11) used immunohistochemistry on mirror sections and image analysis to demonstrate colocalization of 11ßHSD2 and MR in a range of human epithelia. It appears from this and previous studies that 11ßHSD2 regulates glucocorticoid and mineralocorticoid actions locally. To better understand the biological role of 11ßHSD2 in the lung, it is important to explore correlations between the distribution of 11ßHSD2 and that of the corticosteroid receptors.

It is well known that cortisol is a prerequisite for the induction of surfactant synthesis (12) and fetal lung maturation (13). Recently, expression of 11ßHSD2 was demonstrated in the homogenized human fetal lung (5, 6), but its localization and possible biological roles remain unknown. Therefore, in this study we examined the immunohistochemical localization of 11ßHSD2, MR, and GR in nonpathological human lung at various stages of development from fetus through to adult to evaluate possible involvement of corticosteroids in human lung maturation and pulmonary function.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Human lung tissues

Forty cases of nonpathological human lung were obtained at elective abortion (8–21 weeks gestation) from Tohoku University Hospital and the affiliated hospitals in Sendai, Japan, or were retrieved from autopsy files of Tohoku University Hospital (22–41 weeks gestation, and 1 day to 55 yr of age). This study protocol was approved by the committee on the ethics of Tohoku University School of Medicine. Lung tissues were fixed in 10% formalin and embedded in paraffin wax. Histological examination revealed no significant pathological abnormalities. Nonpathological human lungs were classified according to the criteria of Carlson (14): pseudoglandular phase (8–16 weeks gestation; n = 6), canalicular phase (17–26 weeks gestation; n = 8), terminal sac phase (26–41 weeks gestation; n = 12), and lungs after birth (1 day to 55 yr of age; n = 14). Immunostaining was performed on serial sections.

Antibody production and characterization

The generation and characterization of the primary antibodies for 11ßHSD2 (HUH23) and MR (MINREC4) have been described previously (7, 15). Briefly, 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 MR. Application of these antibodies to immunohistochemistry was reported previously (11, 16). Monoclonal antibody for GR (NCL-GCR) was purchased from Novocastra Laboratories (Newcastle, UK).

Immunohistochemistry

Immunohistochemical analyses were performed employing the streptavidin-biotin amplification method using a Histofine Kit (Nichirei, Tokyo, Japan) and were described in detail previously (16, 17). For GR immunostaining, the slides were heated in an autoclave at 120 C for 5 min in citric acid buffer (2 mmol/L citric acid and 9 mmol/L trisodium citrate dehydrate, pH 6.0) after deparaffinization. The HUH23 antibody was used at a final concentration of 5 µg/mL, MINREC4 was used at a dilution of 1:600, and NCL-GCR was diluted 1:100. The antigen-antibody complex was visualized with 3,3'-diaminobenzidine solution [1 mmol/L 3,3'-diaminobenzidine, 50 mmol/L Tris-HCl buffer (pH 7.6), and 0.006% H2O2] and counterstained with methyl green. Tissue sections of normal kidney obtained at autopsy were used as positive controls for 11ßHSD2 and MR (11), and those of lung carcinomas were used for GR (18). For negative controls, preimmune rabbit serum or normal mouse IgG was used instead of the primary antibodies, and no specific immunoreactivity was detected in these sections.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The results of immunohistochemical staining of 11ßHSD2, MR, and GR in nonpathological human lungs are summarized in Table 1Go. 11ßHSD2 immunoreactivity was present in the cytoplasm, and MR immunoreactivity was detected predominantly in the cytoplasm with some nuclear staining. GR immunoreactivity was present in the nuclei of all cell types in all specimens of human lung examined in this study.


View this table:
[in this window]
[in a new window]
  		Table 1. Immunohistochemical localization of 11ßHSD2, MR, and GR in nonpathological human lungs

 
In the pseudoglandular phase of fetal lungs, both 11ßHSD2 and MR immunoreactivities were detected weakly in bronchi lined by columnar epithelia with marked variations in their immunointensity, but staining was not detected in mesenchymal cells. In the canalicular phase, 11ßHSD2 and MR immunoreactivities were present in terminal bronchiolar budding components (respiratory bronchioles) lined by columnar epithelia, but was not detected in other components of terminal bronchioles or loose mesenchymal cells (Fig. 1AGo). 11ßHSD2 and MR immunoreactivities were marked in bronchi and trachea lined by ciliated epithelia and ciliated collecting ducts of bronchial and tracheal glands, but was not present in the acinar cells (Fig. 1Go, B and C). In the terminal sac phase, 11ßHSD2 and MR immunoreactivities were widely distributed in ciliated epithelia from terminal bronchiole to trachea, but were not present in alveoli (Fig. 2Go, A and B). The distribution of 11ßHSD2 and MR in lungs after birth was the same as that in the terminal sac phase in fetal lungs. However, the relative immunointensity of 11ßHSD2 and MR in lungs after birth, especially in the proximal airway, tended to be weaker than that in the terminal sac phase, although variations in the immunointensity were observed (Table 1Go).



View larger version (99K):
[in this window]
[in a new window]
  		Figure 1. Immunohistochemistry of 11ßHSD2 (A and B) and MR (C) in canalicular phase fetal lung (21 weeks gestation). A, Immunoreactivity of 11ßHSD2 was observed in budding terminal components of bronchioles (respiratory bronchioles) lined by columnar epithelia (arrows), whereas other components of terminal bronchioles or loose mesenchymal cells were negative for 11ßHSD2 (original magnification, x245). 11ßHSD2 (B) and MR (C) immunoreactivities were detected in trachea lined by ciliated epithelia and collecting ciliated duct of the tracheal gland (arrow), but was not detected in the acinar cells (original magnification, x178, respectively).

 


View larger version (124K):
[in this window]
[in a new window]
  		Figure 2. Immunohistochemistry of 11ßHSD2 (A) and GR (B) in terminal sac phase fetal lung (31 weeks gestation). A, 11ßHSD2 immunoreactivity was detected in ciliated epithelia from terminal bronchiole to trachea, but was not present in alveoli (original magnification, x178). B, GR immunoreactivity was present in the nuclei of all cell types including bronchioles and alveoli (original magnification, x245).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Glucocorticoids have been demonstrated to play important roles not only in the structural development of organs but also in the maturation and programming of homeostatic systems (19, 20). However, excessive glucocorticoid can be harmful to the developing fetus, resulting in reduced birth weight and predisposition to hypertension in adulthood (21). The ratio of plasma cortisol/cortisone is approximately 10:1 in the adult, but is only 1:2 in the fetus (22). Expression of 11ßHSD2 was reported in the human placenta and various fetal tissues, including lung (1, 4, 5, 6). These findings suggest that 11ßHSD2 may serve to modulate biologically active glucocorticoid concentrations in fetal organs in an autocrine fashion (5). Human lung is a classical glucocorticoid target tissue (6), and cortisol plays an important role in surfactant synthesis by type II pneumocytes in alveoli (12). Therefore, it was possible that the 11ßHSD2 present in alveoli of terminal sac phase of the fetal lungs was involved in the regulation of glucocorticoid actions in type II pneumocytes. However, the results of our present study demonstrate that 11ßHSD2 was present in epithelial cells of the airway in fetal lungs from pseudoglandular to terminal sac phases, but not in the alveoli, throughout the course of lung development. In addition, 11ßHSD2 immunoreactivity colocalized with MR to specific cell types, whereas GR immunoreactivity was detected in all cell types of the human lung. Krozowski and Funder (23) previously demonstrated the presence of mineralocorticoid-specific high affinity [3H]aldosterone-binding sites in the adult rat lung and suggested that some cell types may be a physiological target for aldosterone via MR in the lung. 11ßHSD2 is thought to confer mineralocorticoid specificity by preempting nonselective binding of cortisol to MR (9, 10) and to modulate access of glucocorticoids to the GR. Hirasawa et al. (11) recently demonstrated that 11ßHSD2 colocalized with MR in sodium-transporting epithelia in adult human tissues. Therefore, the results of our present study suggest that 11ßHSD2 plays an important role in the regulation of mineralocorticoid action, i.e. sodium and fluid absorption, in human fetal airway, rather than in the modulation of glucocorticoid activity.

Little is known about the effects of mineralocorticoid in the fetal lung, although this organ contains fluid at all stages of intrauterine development. Lung liquid is not aspirated amniotic fluid, but is actively produced by the fetal lung itself (24). Fetal pulmonary development is dependent on lung fluid to maintain distention, and the retention of liquid within the developing airway is required to adequately expand the lungs to stimulate their growth (25). Various studies have demonstrated that the fetal lung can function as both a fluid-absorbing and a fluid-secreting organ (26, 27, 28). In our study, immunoreactivity of 11ßHSD2 and MR was strongest in the columnar epithelium of the respiratory bronchiole, the ciliated tracheal and bronchial epithelium in the canalicular phase, and the ciliated epithelium from bronchiole to trachea in the terminal sac phase. Therefore, 11ßHSD2 and MR may be important for active fluid absorption at these sites and may also contribute to the local regulation of lung liquid.

The distribution of 11ßHSD2 and MR in neonatal lung was in good agreement with the report by Hirasawa et al. (11) and was the same as that observed in the terminal sac phase in fetal lungs. Page et al. (29) demonstrated 11ßHSD2 activity in human lung cells, and Cullen and Welsh (30) also reported that sodium absorption is both acutely and chronically regulated by mineralocorticoids in the canine tracheal epithelium. These findings together with our present data suggest that 11ßHSD2 is also involved in the modulation of mineralocorticoid action in airway epithelia after birth. Immediately postpartum the lungs are cleared of lung liquid and function as an organ of gas exchange. However, secretions form tracheal and bronchial glands cover the entire surface of the respiratory tract and facilitate mucosal cell function. Therefore, 11ßHSD2 may also regulate secretion in the respiratory tract after birth. Variations in relative 11ßHSD2 and MR immunointensity in the lungs after birth may represent the influence of various exogenous factors, but further investigations are required to clarify their biological significance.

Received May 12, 1998.

Revised July 17, 1998.

Accepted July 22, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Brown RW, Chapman KE, Edwards CRW, Seckl JR. 1993 Human placental 11ß-hydroxysteroid dehydrogenase: evidence for and partial purification of a distinct NAD-dependent isoform. Endocrinology. 132:2614–2621.[Abstract/Free Full Text]
  2. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS. 1994 Cloning and tissue distribution of the human 11ß-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol. 105:R11–R17.
  3. Mune T, Rogerson FM, Nikkila H, Agarwal AK, White PC. 1995 Human hypertension caused by mutations in the kidney isozymes of 11ß-hydroxysteroid dehydrogenase. Nat. Genet. 10:394–399.
  4. Murphy BEP. 1981 Ontogeny of cortisol-cortisone interconversion in human tissues: a role of cortisone in human fetal development. J Steroid Biochem. 14:811–817.[CrossRef][Medline]
  5. Stewart PM, Murry BA, Mason JI. 1994 Type 2 11ß-hydroxysteroid dehydrogenase in human fetal tissues. J Clin Endocrinol Metab. 78:1529–1532.[Abstract]
  6. Stewart PM, Whorwood CB, Mason JI. 1995 Type 2 11ß-hydroxysteroid dehydrogenase in foetal and adult life. J Steroid Biochem Mol Biol. 55:465–471.[CrossRef][Medline]
  7. Krozowski ZS, MaGuire JA, Stein-Oakley AN, Dowling J, Smith RE, Andrews RK. 1995 Immunohistochemical localization of the 11ß-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta. J Clin Endocrinol Metab. 80:2203–2209.[Abstract]
  8. Smith RE, Maguire JA, Stein-Oakley AN, et al. 1996 Localization of 11ß-hydroxysteroid dehydrogenase type II in human epithelial tissues. J Clin Endocrinol Metab. 81:3244–3248.[Abstract]
  9. Edwards CR, Stewart PM, Burt D, et al. 1988 Localization of 11ß-hydroxysteroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor. Lancet. 2:986–989.[CrossRef][Medline]
  10. 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]
  11. Hirasawa G, Sasano H, Takahashi K, et al. 1997 Colocalization of 11ß-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia. J Clin Endocrinol Metab. 82:3859–3863.[Abstract/Free Full Text]
  12. Hundertmark S, Buhler H, Ragosch V, Dinkelborg L, Arabin B, Weitzel HK. 1995 Correlation of surfactant phosphatidylcholine synthesis and 11ß-hydroxysteroid dehydrogenase in the fetal lung. Endocrinology. 136:2573–2578.[Abstract]
  13. Pepe GJ, Albrecht ED. 1995 Actions of fetal adrenal steroid hormones in primate pregnancy. Endocr Rev. 16:608–648.[Abstract/Free Full Text]
  14. Carlson BM. 1994 Human embryology and developmental biology. St Louis: Mosby; 325–328.
  15. 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/Free Full Text]
  16. 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/Free Full Text]
  17. Suzuki T, Sasano H, Kimura N, et al. 1994 Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes. Hum Reprod. 9:1589–1595.[Abstract/Free Full Text]
  18. Kaiser U, Hofmann J, Schilli M, et al. 1996 Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer. Int J Cancer. 67:357–364.[CrossRef][Medline]
  19. Seckl JR, Brown RW. 1994 11ß-Hydroxysteroid dehydrogenase: on several roads to hypertension. J Hypertension. 12:105–112.[Medline]
  20. Cole TJ, Blendy JA, Monaghan AP, et al. 1995 Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 9:1608–1621.[Abstract/Free Full Text]
  21. Edwards CRW, Benediktson R, Lindsay RS, Seckl JR. 1993 Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet. 341:355–357.[CrossRef][Medline]
  22. Whitworth JA, Stewart PM, Burt D, Atherden SM, Edwards CRW. 1988 The kidney is the major site of cortisone production in man. Clin Endocrinol (Oxf). 31:355–361.
  23. Krozowski Z, Funder JW. 1981 Mineralocorticoid receptors in the rat lung. Endocrinology. 109:1811–1813.[Abstract/Free Full Text]
  24. Harding R, Bocking AD, Sigger JN. 1986 Influence of upper respiratory tract on liquid flow to and from fetal lungs. J Appl Physiol. 61:68–74.[Abstract/Free Full Text]
  25. Hooper SB, Harding R. 1995 Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung. Clin Exp Pharmacol Physiol. 22:235–247.[Medline]
  26. Yankaskas JR, Boucher RC. 1990 Ion transport properties of human fetal tracheal epithelial cells in primary culture [Abstract]. Am Rev Respir Dis. 141:A163.
  27. Rao AK, Cott GR. 1991 Ontogeny of ion transport across fetal pulmonary epithelial cells in monolayer culture. Am J Physiol. 261:L178–L187.
  28. O’Brodovich H. 1991 Epithelial ion transport in the fetal and perinatal lung. Am J Physiol. 261:C555–C564.
  29. Page N, Warriar N, Govindan MV. 1994 11ß-Hydroxysteroid dehydrogenase activity in human lung cells and transcriptional regulation by glucocorticoids. Am J Physiol. 267:L464–L474.
  30. Cullen JJ, Welsh MJ. 1987 Regulation of sodium absorption by canine tracheal epithelium. J Clin Invest. 79:73–79.



This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
M. Schroth, C. Plank, M. Rauh, H.-G. Dorr, W. Rascher, and J. Dotsch
Pediatric renal allograft transplantation does not normalize the increased cortisol/cortisone ratios of chronic renal failure.
Eur. J. Endocrinol., April 1, 2006; 154(4): 555 - 561.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
M. Keller-Wood, C. E. Wood, Y. Hua, and D. Zhang
Mineralocorticoid Receptor Expression in Late-Gestation Ovine Fetal Lung
Reproductive Sciences, February 1, 2005; 12(2): 84 - 91.
[Abstract] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. J. Cole, N. M. Solomon, R. Van Driel, J. A. Monk, D. Bird, S. J. Richardson, R. J. Dilley, and S. B. Hooper
Altered Epithelial Cell Proportions in the Fetal Lung of Glucocorticoid Receptor Null Mice
Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 613 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Suzuki, K. Koyama, A. Darnel, H. Ishibashi, S. Kobayashi, H. Kubo, T. Suzuki, H. Sasano, and Z. S. Krozowski
Dexamethasone Upregulates 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in BEAS-2B Cells
Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1244 - 1249.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Mune, H. Morita, T. Suzuki, Y. Takahashi, Y. Isomura, T. Tanahashi, H. Daido, N. Yamakita, T. Deguchi, H. Sasano, et al.
Role of Local 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Expression in Determining the Phenotype of Adrenal Adenomas
J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 864 - 870.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. J. Pepe, P. L. Ballard, and E. D. Albrecht
Fetal Lung Maturation in Estrogen-Deprived Baboons
J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 471 - 477.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 Physiol. Rev.Home page
M. A. Matthay, H. G. Folkesson, and C. Clerici
Lung Epithelial Fluid Transport and the Resolution of Pulmonary Edema
Physiol Rev, July 1, 2002; 82(3): 569 - 600.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
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]

Home page
 J. Biol. Chem.Home page
D. Le Menuet, R. Isnard, M. Bichara, S. Viengchareun, M. Muffat-Joly, F. Walker, M.-C. Zennaro, and M. Lombes
Alteration of Cardiac and Renal Functions in Transgenic Mice Overexpressing Human Mineralocorticoid Receptor
J. Biol. Chem., October 12, 2001; 276(42): 38911 - 38920.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
G.A.W. Rook, G. Seah, and A. Ustianowski
M. tuberculosis: immunology and vaccination
Eur. Respir. J., March 1, 2001; 17(3): 537 - 557.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. W. BAKER, B. R. WALKER, R. J. SHAW, J. W. HONOUR, D. S. JESSOP, S. L. LIGHTMAN, A. ZUMLA, and G. A. W. ROOK
Increased Cortisol . Cortisone Ratio in Acute Pulmonary Tuberculosis
Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1641 - 1647.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Suzuki, T.
Right arrow Articles by Krozowski, Z. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, T.
Right arrow Articles by Krozowski, Z. S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals