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Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11β-hydroxysteroid dehydrogenase type 1
Open accessAbstract
Two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) interconvert active cortisol and inactive cortisone. 11β-HSD2 (renal) acts only as a dehydrogenase, converting cortisol to cortisone. 11β-HSD1 (liver) is a bi-directional enzyme in cell homogenates, whereas in intact cells it typically displays oxo-reductase activity, generating cortisol from cortisone. We recently established that cortisone reductase deficiency is a digenic disease requiring mutations in both the gene encoding 11β-HSD1 and in the gene for a novel enzyme located within the lumen of the endoplasmic reticulum (ER), hexose-6-phosphate dehydrogenase (H6PDH). This latter enzyme generates NADPH, the co-factor required for oxo-reductase activity. Therefore, we hypothesized that H6PDH expression may be an important determinant of 11β-HSD1 oxo-reductase activity. Transient transfection of chinese hamster ovary (CHO) cells with 11β-HSD1 resulted in the appearance of both oxo-reductase and dehydrogenase activities in intact cells. Co-transfection of 11β-HSD1 with H6PDH increased oxo-reductase activity whilst virtually eliminating dehydrogenase activity. In contrast, H6PDH had no effect on reaction direction of 11β-HSD2, nor did the cytosolic enzyme, glucose-6-phosphate dehydrogenase (G6PD) affect 11β-HSD1 oxo-reductase activity. Conversely in HEK 293 cells stably transfected with 11β-HSD1 cDNA, transfection of an H6PDH siRNA reduced 11β-HSD1 oxo-reductase activity whilst simultaneously increasing 11β-HSD1 dehydrogenase activity. In human omental preadipocytes obtained from 15 females of variable body mass index (BMI), H6PDH mRNA levels positively correlated with 11β-HSD1 oxo-reductase activity, independent of 11β-HSD1 mRNA levels. H6PDH expression increased 5.3-fold across adipocyte differentiation (P<0.05) and was associated with a switch from 11β-HSD1 dehydrogenase to oxo-reductase activity. In conclusion, H6PDH is a crucial determinant of 11β-HSD1 oxo-reductase activity in intact cells. Through its interaction with 11β-HSD1, H6PDH may represent a novel target in the pathogenesis and treatment of obesity.
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“as colocalized hexose-6-phosphate dehydrogenase (H6PDH) regenerates NADPH required for its cortisone reductase activity”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [109]
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“HSD11B1 is a bidirectional enzyme, but primarily catalyzes the reduction of 11-ketosteroids in vivo”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [109]
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“mainly activating cortisone to cortisol [109]”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [109]
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Cites
A JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Lindemann, L., Jaeschke, G., Michalon, A., Vieira, E., Honer, M., Spooren, W., Porter, R., Hartung, T., Kolczewski, S., Büttelmann, B., et al. (1909) · JAMA · doi:10.1001/jama.1909.02550020033007 · Cited by 7,889
Biochemical and Biophysical Research Communications
Rc, A. N., On Filamentous Bacteriophage, M., Hoffmann, S., & Willbold, D. (1960) · Nature · doi:10.1038/186124d0 · Cited by 6,690
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Hoskins, R. G. (1953) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-13-4-473 · Cited by 3,780
Investigative Ophthalmology and Visual Science
Frey, C. (2010) · Cited by 3,350
A transgenic model of visceral obesity and the metabolic syndrome
Masuzaki, H., Paterson, J., Shinyama, H., Morton, N. M., Mullins, J. J., Seckl, J. R., & Flier, J. S. (2001) · Science · doi:10.1126/science.1066285 · Cited by 1,766
The Journal of Steroid Biochemistry and Molecular Biology
(2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(11)00143-9 · Cited by 1,233
Does central obesity reflect “Cushing's disease of the omentum”?
Bujalska, I. J., Kumar, S., & Stewart, P. M. (1997) · The Lancet · doi:10.1016/s0140-6736(96)11222-8 · Cited by 753
Self-citationTissue-Specific Dysregulation of Cortisol Metabolism in Human Obesity
Rask, E., Olsson, T., Söderberg, S., Andrew, R., Livingstone, D. E. W., Johnson, O., & Walker, B. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7453 · Cited by 657
Cloning and expression of rat cDNA encoding corticosteroid 11β-dehydrogenase
Agarwal, A. K., Monder, C., Eckstein, B., & White, P. C. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47248-7 · Cited by 455
Self-citationPaterson, J. M., Morton, N. M., Fiévet, C., Kenyon, C. J., Holmes, M. C., Staels, B., Seckl, J. R., & Mullins, J. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305524101 · Cited by 430
Stewart, P. M., Boulton, A., Kumar, S., Clark, P. M. S., & Shackleton, C. H. L. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.3.5538 · Cited by 398
Self-citationLakshmi, V. M., & Monder, C. (1988) · Endocrinology · doi:10.1210/endo-123-5-2390 · Cited by 312
Hauner, H., Schmid, P., & PFEIFFER, E. F. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-4-832 · Cited by 312
Jamieson, P. M., Chapman, K. E., Edwards, C. R. W., & Seckl, J. R. (1995) · Endocrinology · doi:10.1210/endo.136.11.7588203 · Cited by 301
Self-citationDraper, N., Walker, E. A., Bujalska, I. J., Tomlinson, J. W., Chalder, S. M., Arlt, W., Lavery, G. G., Bedendo, O., Ray, D. W., Laing, I., et al. (2003) · Nature Genetics · doi:10.1038/ng1214 · Cited by 285
Self-citationAndrews, R. C., Rooyackers, O., & Walker, B. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021194 · Cited by 264
Alberts, P., Nilsson, C., Selén, G., Engblom, L. O. M., Edling, N. H. M., Norling, S., Klingström, G., Larsson, C., Forsgren, M., Ashkzari, M., et al. (2003) · Endocrinology · doi:10.1210/en.2003-0344 · Cited by 263
Muscle and Adipose Tissue Morphology and Metabolism in Cushing’s Syndrome*
Rebuffé-Scrive, M., Krotkiewski, M., Elfverson, J., & Björntorp, P. A. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-6-1122 · Cited by 262
Alberts, P., Engblom, L. I., Edling, N. H. M., Forsgren, M., Klingström, G., Larsson, C., Rönquist-Nii, Y., Öhman, B., & Abrahmsén, L. (2002) · Diabetologia · doi:10.1007/s00125-002-0959-6 · Cited by 259
Bujalska, I. J., Kumar, S., Hewison, M., & Stewart, P. M. (1999) · Endocrinology · doi:10.1210/endo.140.7.6868 · Cited by 258
Self-citationSandeep, T. C., Yau, J. L. W., MacLullich, A. M. J., Noble, J., Deary, I. J., Walker, B. R., & Seckl, J. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306996101 · Cited by 246
Persico, M. G., Viglietto, G., Martini, G., Toniolo, D., Paonessa, G., Moscatelli, C., Dono, R., Vulliamy, T., Luzzatto, L., & D’Urso, M. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.6.2511 · Cited by 244
Wake, D. J., Rask, E., Livingstone, D. E. W., Söderberg, S., Olsson, T., & Walker, B. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030286 · Cited by 228
Atanasov, A. G., Nashev, L. G., Schweizer, R. A. S., Frick, C., & Odermatt, A. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.06.065 · Cited by 208
Cloning and production of antisera to human placental 11 β-hydroxysteroid dehydrogenase type 2
BROWN, R. W., Chapman, K. E., Kotelevtsev, Y. V., Yau, J. L. W., LINDSAY, R. S., Brett, L. P., Leckie, C. M., MURAD, P., Lyons, V., Mullins, J. J., et al. (1996) · Biochemical Journal · doi:10.1042/bj3131007 · Cited by 198
Self-citationImmunohistochemical Localization of Type 1 11β-Hydroxysteroid Dehydrogenase in Human Tissues1
Ricketts, M., Verhaeg, J. M., Bujalska, I. J., Howie, A. J., Rainey, W. E., & Stewart, P. M. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.4.4706 · Cited by 197
Self-citationOdermatt, A., Arnold, P., Stauffer, A., Frey, B. M., & Frey, F. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.40.28762 · Cited by 190
Tomlinson, J., Sinha, B., Bujalska, I. J., Hewison, M., & Stewart, P. M. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020687 · Cited by 187
Self-citationBánhegyi, G., Benedetti, A., Fulceri, R., & Senesi, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404159200 · Cited by 170
Bujalska, I. J., Walker, E. A., Hewison, M., & Stewart, P. M. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.3.8301 · Cited by 157
Self-citationExpression of 11β-hydroxysteroid dehydrogenase using recombinant vaccinia virus
Agarwal, A. K., Tusie-Luna, M.-T., Monder, C., & White, P. C. (1990) · Molecular Endocrinology · doi:10.1210/mend-4-12-1827 · Cited by 155
Self-citationExpression and functional consequences of 11β-hydroxysteroid dehydrogenase activity in human bone
Cooper, M. S., Walker, E. A., Bland, R., Fraser, W. D., Hewison, M., & Stewart, P. M. (2000) · Bone · doi:10.1016/s8756-3282(00)00344-6 · Cited by 154
Self-citationGe, R., Gao, H.-B., Nacharaju, V. L., Gunsalus, G. L., & Hardy, M. P. (1997) · Endocrinology · doi:10.1210/endo.138.6.5165 · Cited by 128
Localization and Characteristics of Hexose 6-Phosphate Dehydrogenase (Glucose Dehydrogenase)
Beutler, E., & Morrison, M. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99426-3 · Cited by 127
Ozols, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.2305 · Cited by 115
C/EBP Regulates Hepatic Transcription of 11β-Hydroxysteroid Dehydrogenase Type 1
Williams, L. J. S., Lyons, V., MacLeod, I., Rajan, V., Darlington, G., Poli, V., Seckl, J. R., & Chapman, K. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001286200 · Cited by 115
Self-citationLow, S. C., Chapman, K. E., Edwards, C. R. W., & Seckl, J. R. (1994) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0130167 · Cited by 108
Self-citationBujalska, I. J., Shimojo, M., Howie, A., & Stewart, P. M. (1997) · Steroids · doi:10.1016/s0039-128x(96)00163-8 · Cited by 100
Self-citationJamieson, A., Wallace, E. M., Andrew, R., Nunez, B. S., Walker, B. R., Fraser, R., White, P. C., & Connell, J. M. C. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6031 · Cited by 100
Self-citationNikkilä, H., Tannin, G. M., New, M. I., Taylor, N., Kalaitzoglou, G., Monder, C., & White, P. C. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.3.8370690 · Cited by 98
Self-citationVoice, M. W., Seckl, J. R., Edwards, C. R. W., & Chapman, K. E. (1996) · Biochemical Journal · doi:10.1042/bj3170621 · Cited by 92
Self-citationLivingstone, D. E. W., & Walker, B. R. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.044842 · Cited by 89
Jamieson, P. M., Walker, B., Chapman, K. E., Andrew, R., Rossiter, S., & Seckl, J. R. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.1650685 · Cited by 86
Self-citationBland, R., Worker, C., Noble, B., Eyre, L. J., Bujalska, I., Mc, S., Stewart, P., & Hewison, M. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1610455 · Cited by 80
Self-citationEvidence for kinetically distinct forms of corticosteroid 11β-dehydrogenase in rat liver microsomes
Monder, C., & Lakshmi, V. M. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90017-4 · Cited by 78
Subcellular Localization of the Type 2 11β-Hydroxysteroid Dehydrogenase
Náray‐Fejes‐Tóth, A., & Fejes‐Tóth, G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.26.15436 · Cited by 75
Rauz, S., Cheung, C. M. G., Wood, P. J., Coca‐Prados, M., Walker, E. A., Murray, P. I., & Stewart, P. (2003) · QJM · doi:10.1093/qjmed/hcg085 · Cited by 75
Self-citationOzols, J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.11.5302 · Cited by 71
Walker, E. A., Clark, A. M., Hewison, M., Ride, J. P., & Stewart, P. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011142200 · Cited by 65
Self-citationA transgenic model of visceral obesity and the metabolic syndrome
Szidonya, L. K., & Hunyady, L. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(02)00581-7 · Cited by 63
Expression and putative role of 11 beta-hydroxysteroid dehydrogenase isozymes within the human eye.
Rauz, S., Walker, E. A., Shackleton, C. H. L., Hewison, M., Murray, P. I., & Stewart, P. M. (2001) · PubMed · Cited by 61
Self-citationThe pentose phosphate pathway in the endoplasmic reticulum.
Bublitz, C., & Steavenson, S. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37638-5 · Cited by 61
11beta-hydroxysteroid dehydrogenase is a predominant reductase in intact rat Leydig cells
Leckie, C., Welberg, L., & Seckl (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1590233 · Cited by 55
Kinetic studies on rat liver 11β-hydroxysteroid dehydrogenase
Monder, C., Lakshmi, V. M., & Miroff, Y. (1991) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(91)90006-3 · Cited by 50
Mason, P. J., Stevens, D., Díez, A., Knight, S. W., Scopes, D. A., & Vulliamy, T. (1999) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.1999.0224 · Cited by 47
Apparent Cortisone Reductase Deficiency: A Rare Cause of Hyperandrogenemia and Hypercortisolism
Biason‐Lauber, A., Suter, S. L., Shackleton, C. H. L., & ZACHMANN, M. (2000) · Hormone Research in Paediatrics · doi:10.1159/000023577 · Cited by 41
Evidence for glucose‐6‐phosphate transport in rat liver microsomes
Gerin, I., & SCHAFTINGEN, E. V. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02640-6 · Cited by 41
Nikkila, H. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.77.3.687 · Cited by 40
Jones, C. G., Hothi, S. K., & Titheradge, M. A. (1993) · Biochemical Journal · doi:10.1042/bj2890821 · Cited by 36
Kimura, K., Endou, H., Jun-ichi, S. U. D. O., & Sakai, F. (1979) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a132336 · Cited by 27
Stegeman, J. J., & Klotz, A. V. (1979) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(79)91811-4 · Cited by 24
Jellinck, P. H., Pavlides, C., Sakai, R. R., & McEwen, B. S. (1999) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(99)00133-8 · Cited by 23
Persico, M. G., Viglietto, G., Martini, G., Toniolo, D., Paonessa, G., Moscatelli, C., Dono, R., Vulliamy, T., Luzzatto, L., & D’Urso, M. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.19.7821 · Cited by 13
Laing, I., Adams, J. B., Wood, P. G., Taylor, N., & Ray, D. W. (2002) · 21st Joint Meeting of the British Endocrine Societies · Cited by 6
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- Kotelevtsev Y , Holmes MC, Burchell A, Houston PM, Schmoll D, Jamieson P, Best R, Brown R, Edwards CR, Seckl JR et al.1997 11 beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. PNAS9414924–14929. · DOI
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Miller, W. L., & Auchus, R. J. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0013 · Cited by 2,458
11β-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action
Chapman, K., Holmes, M., & Seckl, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00020.2012 · Cited by 887
Self-citationSchiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450
Lavery, G. G., Walker, E. A., Draper, N., Jeyasuria, P., Marcos, J., Shackleton, C. H. L., Parker, K. L., White, P. C., & Stewart, P. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512635200 · Cited by 207
Self-citationStorbeck, K.-H., Bloem, L. M., Africander, D., Schloms, L., Swart, P., & Swart, A. C. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.07.006 · Cited by 198
Metadata
- Authors
- Bujalska, I. J., Draper, N., Michailidou, Z., Tomlinson, J. W., White, P. C., Chapman, K. E., Walker, E. A., & Stewart, P. M.
- Affiliations
- University of Birmingham (GB)
- Western General Hospital (GB)
- The University of Texas Southwestern Medical Center (US)
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 2005-06-01
- Volume
- 34
- Issue
- 3
- Pages
- 675-684
- ISSN
- 0952-5041 (ISSN-L)
- 1479-6813
- OpenAlex
- W2145137221
- Semantic Scholar
- ea6c19382d7728e2ab3b59c90109625c30738483
- Cited by
- 165
- References
- 65
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 10 · 2013: 10 · 2012: 6
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Imperial College London
- Medical Research Council
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- hexose-6-phosphate dehydrogenase, NADPH, endoplasmic reticulum, cortisol metabolism, cortisone, glucose-6-phosphate dehydrogenase, adipogenesis, preadipocytes, siRNA knockdown, isozymes, body mass index
- MeSH terms
- Adult, Animals, Base Sequence, Carbohydrate Dehydrogenases, Female, Cricetinae, Humans, RNA, Messenger, Blotting, Western, Polymerase Chain Reaction, CHO Cells, DNA Primers, RNA, Small Interfering, 11-beta-Hydroxysteroid Dehydrogenase Type 1
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