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Journal of Clinical Endocrinology & Metabolism, Vol 80, 2203-2209, Copyright © 1995 by Endocrine Society


ARTICLES

Immunohistochemical localization of the 11 beta-hydroxysteroid dehydrogenase type II enzyme in human kidney and placenta

Z Krozowski, JA MaGuire, AN Stein-Oakley, J Dowling, RE Smith and RK Andrews
Laboratory of Molecular Hypertension, Baker Institute of Medical Research, Prahran, Australia.

It has been proposed that the inactivation of glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) is an obligatory step in the kidney, permitting binding of aldosterone to the mineralocorticoid receptor, and in the placenta, protecting the fetus from high circulating levels of maternal glucocorticoids. Both low and high affinity isoforms of 11 beta HSD are known to exist, with evidence accumulating that the former species (11 beta HSD1) does not fulfill criteria that would allow it to perform these physiological functions. We have recently cloned a high affinity isoform of the enzyme (11 beta HSD2) from a human kidney library and have shown this species to possess all of the characteristics predicted from whole cell studies. In the present study we have raised a polyclonal antibody (HUH23) to a synthetic peptide deduced from the carboxy-terminus of the protein. The immunopurified antibody recognized a single band at 41,000 daltons on Western blots of mammalian cells transfected with an expression plasmid containing 11 beta HSD2, slightly smaller than the predicted 44,140 daltons protein. A single band of identical size was also seen in blots of human kidney and placenta, suggesting post-translational processing of the enzyme. Immunohistochemical studies on frozen sections of human kidney showed strong 11 beta HSD2 immunoreactivity in the cortical distal convoluted tubules and collecting ducts. Strong staining was also observed in medullary tubules, which had the appearance of collecting ducts and the thick ascending limb of Henle's loop. Staining of medium intensity was observed in vascular smooth muscle cells. Epithelial cells of glomeruli showed weak but detectable reactivity with HUH23. In the placenta, HUH23 antibody immunoreactivity was restricted to syncytial trophoblast cells in which strong staining was observed. These results suggest that the 11 beta HSD2 enzyme colocalizes with the mineralocorticoid receptor in the distal nephron where it allows aldosterone to occupy its physiological receptor. Furthermore, 11 beta HSD2 is also ideally situated in the placenta to protect the fetus from high circulating levels of maternal glucocorticoids.


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EndocrinologyHome page
K. X. Z. Li, V. R. Obeyesekere, Z. S. Krozowski, and P. Ferrari
Oxoreductase and Dehydrogenase Activities of the Human and Rat 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Enzyme
Endocrinology, July 1, 1997; 138(7): 2948 - 2952.
[Abstract] [Full Text] [PDF]


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Reproductive SciencesHome page
J. Bissonnette, S. Chambers, P. Collins, C. Lockwood, C. Mendelson, L. Myatt, M. L. Polan, W. H. Shen, and S. Szal
Strengthening Research in Departments of Obstetrics and Gynecology
Reproductive Sciences, May 1, 1997; 4(3): 124 - 129.
[Abstract] [PDF]


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EndocrinologyHome page
M. Shimojo, M. L. Ricketts, M. D. Petrelli, P. Moradi, G. D. Johnson, A. R. Bradwell, M. Hewison, A. J. Howie, and P. M. Stewart
Immunodetection of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in Human Mineralocorticoid Target Tissues: Evidence for Nuclear Localization
Endocrinology, March 1, 1997; 138(3): 1305 - 1311.
[Abstract] [Full Text] [PDF]


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Endocr. Rev.Home page
P. C. White, T. Mune, and A. K. Agarwal
11{beta}-Hydroxysteroid Dehydrogenase and the Syndrome of Apparent Mineralocorticoid Excess
Endocr. Rev., February 1, 1997; 18(1): 135 - 156.
[Abstract] [Full Text]


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EndocrinologyHome page
R. E. Smith, K. X. Z. Li, R. K. Andrews, and Z. Krozowski
Immunohistochemical and Molecular Characterization of the Rat 11{beta}-Hydroxysteroid Dehydrogenase Type II Enzyme
Endocrinology, February 1, 1997; 138(2): 540 - 547.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
K. Sun, K. Yang, and J. R. G. Challis
Differential Expression of 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2 in Human Placenta and Fetal Membranes
J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 300 - 305.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
Y. H. Lo, M. F. Sheff, S. A. Latif, C. Ribeiro, H. Silver, A. S. Brem, and D. J. Morris
Kidney 11{beta}-HSD2 Is Inhibited by Glycyrrhetinic Acid-Like Factors in Human Urine
Hypertension, January 1, 1997; 29(1): 500 - 505.
[Abstract] [Full Text] [PDF]


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Physiol. GenomicsHome page
L.-L. HSIAO, F. DANGOND, T. YOSHIDA, R. HONG, R. V. JENSEN, J. MISRA, W. DILLON, K. F. LEE, K. E. CLARK, P. HAVERTY, et al.
A compendium of gene expression in normal human tissues
Physiol Genomics, December 21, 2001; 7(2): 97 - 104.
[Abstract] [Full Text] [PDF]




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