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Original Articles |
Departments of Medicine and Pathology, University of Birmingham, Queen Elizabeth Hospital (A.J.H.), Edgbaston, Birmingham, United Kingdom B15 2TH; and the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center (W.E.R.), Dallas, Texas 75235-7200
Address all correspondence and requests for reprints to: Prof. Paul M. Stewart, M.D., F.R.C.P., Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom B15 2TH. E-mail: p.m.stewart{at}bham.ac.uk
Abstract
Two isozymes of 11ß-hydroxysteroid dehydrogenase (11ßHSD) catalyze the interconversion of hormonally active cortisol to inactive cortisone. Activity and messenger ribonucleic acid studies indicate that type 1 11ßHSD (11ßHSD1) is expressed in glucocorticoid target tissues such as liver, gonad, and cerebellum, where it regulates the exposure of cortisol to glucocorticoid receptors. To further understand the role of 11ßHSD1 in human tissues, we have studied the localization of this isozyme using an antibody raised in sheep against amino acids 19–33 of human 11ßHSD1. Western blot analyses indicated that the immunopurified antibody recognized a band of approximately 34 kDa in human liver and decidua. Immunoperoxidase studies on liver, adrenal, ovary, decidua, and adipose tissue indicated positive cytoplasmic staining for 11ßHSD1. 11ßHSD1 immunoreactivity was observed more intensely around the hepatic central vein, with no staining around the portal vein, hepatic artery, or bile ducts. No staining for 11ßHSD1 was observed in the adrenal medulla, but 11ßHSD1-immunoreactive protein was observed in all three zones of the adrenal cortex, with the most intense staining in the zona reticularis > zona glomerulosa > zona fasciculata. In the human ovary, immunoreactivity was observed in the developing oocyte and the luteinized granulosa cells of the corpus luteum. No staining was observed in granulosa cells, thecal cells, or ovarian stroma, which contrasted with the marked expression of 11ßHSD2 in the granulosa cell layer. Sections of human decidua showed high expression of 11ßHSD1 in decidual cells. In omental adipose tissue, 11ßHSD1 immunoreactivity was observed in both stromal and adipocyte cells. Immunohistochemical localization of 11ßHSD1 in human liver, adrenal, ovary, decidua, and adipose tissue using this novel antiserum provides us with a tool to investigate the role of this isozyme in modulating glucocorticoid hormone action within these tissues.
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N. Draper, S. M. Echwald, G. G. Lavery, E. A. Walker, R. Fraser, E. Davies, T. I. A. Sorensen, A. Astrup, J. Adamski, M. Hewison, et al. Association Studies between Microsatellite Markers within the Gene Encoding Human 11{beta}-Hydroxysteroid Dehydrogenase Type 1 and Body Mass Index, Waist to Hip Ratio, and Glucocorticoid Metabolism J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4984 - 4990. [Abstract] [Full Text] [PDF]
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O. Paulmyer-Lacroix, S. Boullu, C. Oliver, M.-C. Alessi, and M. Grino Expression of the mRNA Coding for 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue from Obese Patients: An in Situ Hybridization Study J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2701 - 2705. [Abstract] [Full Text] [PDF]
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I. J. Bujalska, E. A. Walker, M. Hewison, and P. M. Stewart A Switch in Dehydrogenase to Reductase Activity of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 upon Differentiation of Human Omental Adipose Stromal Cells J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1205 - 1210. [Abstract] [Full Text] [PDF]
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J. W. Tomlinson, N. Draper, J. Mackie, A. P. Johnson, G. Holder, P. Wood, and P. M. Stewart Absence of Cushingoid Phenotype in a Patient with Cushing's Disease due to Defective Cortisone to Cortisol Conversion J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 57 - 62. [Abstract] [Full Text] [PDF]
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 S. Rauz, E. A. Walker, C. H. L. Shackleton, M. Hewison, P. I. Murray, and P. M. Stewart Expression and Putative Role of 11{beta}-Hydroxysteroid Dehydrogenase Isozymes within the Human Eye Invest. Ophthalmol. Vis. Sci., August 1, 2001; 42(9): 2037 - 2042. [Abstract] [Full Text] [PDF]
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M. Korbonits, I. Bujalska, M. Shimojo, J. Nobes, S. Jordan, A. B. Grossman, and P. M. Stewart Expression of 11{beta}-Hydroxysteroid Dehydrogenase Isoenzymes in the Human Pituitary: Induction of the Type 2 Enzyme in Corticotropinomas and Other Pituitary Tumors J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2728 - 2733. [Abstract] [Full Text] [PDF]
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 P.M. Driver, M.D. Kilby, I. Bujalska, E.A. Walker, M. Hewison, and P.M. Stewart Expression of 11{beta}-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies Mol. Hum. Reprod., April 1, 2001; 7(4): 357 - 363. [Abstract] [Full Text] [PDF]
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P. S. Brereton, R. R. van Driel, F. b. H. Suhaimi, K. Koyama, R. Dilley, and Z. Krozowski Light and Electron Microscopy Localization of the 11{beta}-Hydroxysteroid Dehydrogenase Type I Enzyme in the Rat Endocrinology, April 1, 2001; 142(4): 1644 - 1651. [Abstract] [Full Text]
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P. Y. K. Yong, K. J. Thong, R. Andrew, B. R. Walker, and S. G. Hillier Development-Related Increase in Cortisol Biosynthesis by Human Granulosa Cells J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4728 - 4733. [Abstract] [Full Text]
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V. Vicennati and R. Pasquali Abnormalities of the Hypothalamic-Pituitary-Adrenal Axis in Nondepressed Women with Abdominal Obesity and Relations with Insulin Resistance: Evidence for a Central and a Peripheral Alteration J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4093 - 4098. [Abstract] [Full Text]
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J. S. Moore, J. P. Monson, G. Kaltsas, P. Putignano, P. J. Wood, M. C. Sheppard, G. M. Besser, N. F. Taylor, and P. M. Stewart Modulation of 11{beta}-Hydroxysteroid Dehydrogenase Isozymes by Growth Hormone and Insulin-Like Growth Factor: In Vivo and In Vitro Studies J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4172 - 4177. [Abstract] [Full Text]
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I. J. Bujalska, S. Kumar, M. Hewison, and P. M. Stewart Differentiation of Adipose Stromal Cells: The Roles of Glucocorticoids and 11{beta}-Hydroxysteroid Dehydrogenase Endocrinology, July 1, 1999; 140(7): 3188 - 3196. [Abstract] [Full Text]
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P. M. Stewart, A. Boulton, S. Kumar, P. M. S. Clark, and C. H. L. Shackleton Cortisol Metabolism in Human Obesity: Impaired Cortisone->Cortisol Conversion in Subjects with Central Adiposity J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 1022 - 1027. [Abstract] [Full Text]
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E. A. Walker, A. M. Clark, M. Hewison, J. P. Ride, and P. M. Stewart Functional Expression, Characterization, and Purification of the Catalytic Domain of Human 11-beta -Hydroxysteroid Dehydrogenase Type 1 J. Biol. Chem., June 8, 2001; 276(24): 21343 - 21350. [Abstract] [Full Text] [PDF]
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