The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Flagged first, then by citations
1 of the 65 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- 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
Cited by
Sorted by citations
Items 101–164 of 164
Biochemistry and physiology of hexose-6-phosphate knockout mice
Zielinska, A. E., Walker, E. A., Stewart, P. M., & Lavery, G. G. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.12.004 · Cited by 20
Self-citationGlucocorticoid metabolism in the bovine cumulus–oocyte complex matured in vitro
TETSUKA, M., Takagi, R., Ambo, N., Myat, T. S., Zempo, Y., & Onuma, A. (2015) · Reproduction · doi:10.1530/rep-15-0363 · Cited by 21
The metabolism of steroids, toxins and drugs by 11β-hydroxysteroid dehydrogenase 1
Zhou, H.-Y., Hu, G., Lian, Q., Morris, D. J., & Ge, R. (2011) · Toxicology · doi:10.1016/j.tox.2011.11.012 · Cited by 20
Woods, C. P., & Tomlinson, J. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-2895-8_16 · Cited by 19
Self-citationSex Differences in Body Fat Distribution
Veilleux, A., & Tchernof, A. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0965-6_5 · Cited by 17
Sharp, V., Thurston, L. M., Fowkes, R. C., & Michael, A. E. (2007) · Reproduction · doi:10.1530/rep-07-0126 · Cited by 18
Bursać, B. N., Djordjevic, A. D., Veličković, N. A., Milutinović, D. V., Petrović, S., Teofilović, A., Gligorovska, L., Preitner, F., Tappy, L., & Matić, G. M. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.04.015 · Cited by 18
Effects of Gonadectomy on Glucocorticoid Metabolism in Obese Zucker Rats
Barat, P., Livingstone, D. E. W., Elferink, C. M. C., McDonnell, C., Walker, B. R., & Andrew, R. (2007) · Endocrinology · doi:10.1210/en.2007-0597 · Cited by 18
2 Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1
Su, X., Vicker, N., & Potter, B. V. L. (2008) · Progress in medicinal chemistry · doi:10.1016/s0079-6468(07)00002-1 · Cited by 17
Sex Differences in Body Fat Distribution
Mansour, M. F., Chan, C.-W. J., Laforest, S., Veilleux, A., & Tchernof, A. (2017) · Springer eBooks · doi:10.1007/978-3-319-52031-5_8 · Cited by 17
Physiological roles of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase
White, P. C., Rogoff, D., & McMillan, D. R. (2008) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e328305e439 · Cited by 15
Self-citationOnyimba, C., Vijapurapu, N., Curnow, J., Khosla, P., Stewart, P. M., Murray, P. I., Walker, E. A., & Rauz, S. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06840 · Cited by 17
Self-citationFujisawa, Y., Nakagawa, Y., Li, R.-S., Liu, Y., & Ohzeki, T. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.07.002 · Cited by 14
Senesi, S., Marcolongo, P., Manini, I., Fulceri, R., Sorrentino, V., Csala, M., Bánhegyi, G., & Benedetti, A. (2008) · Journal of Molecular Endocrinology · doi:10.1677/jme-08-0028 · Cited by 14
Webb, R. J., Sunak, N., Wren, L. M., & Michael, A. E. (2008) · Reproduction · doi:10.1530/rep-08-0289 · Cited by 14
Biomarkers of hypothalamic–pituitary–adrenal axis activity in mice lacking 11β-HSD1 and H6PDH
Abrahams, L., Semjonous, N. M., Guest, P., Zielinska, A. E., Hughes, B. A., Lavery, G. G., & Stewart, P. M. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0178 · Cited by 14
Self-citationJonas, K., Chandras, C., Abayasekara, D. R. E., & Michael, A. E. (2006) · Endocrinology · doi:10.1210/en.2006-0723 · Cited by 14
Evidence for a role of sterol 27-hydroxylase in glucocorticoid metabolism in vivo
Vögeli, I., Jung, H. H., Dick, B., Erickson, S. K., Escher, R., Funder, J. W., Frey, F. J., & Escher, G. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0141 · Cited by 11
Morales, M., Carvajal, C. A., Ortiz, E., Mosso, L. M., Artigas, R., Owen, G. I., & Fardella, C. (2008) · Revista médica de Chile · doi:10.4067/s0034-98872008000600003 · Cited by 12
Michas, G., Liberman, M., Becker, K. C., Handy, D. E., Loscalzo, J., & Leopold, J. A. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-010-0592-5 · Cited by 11
Sharp, V., Thurston, L. M., Fowkes, R. C., & Michael, A. E. (2009) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2009.03.009 · Cited by 11
McCormick, K. L., Wang, X., & Mick, G. J. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.04.003 · Cited by 11
Auchus, R. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00008-9 · Cited by 11
Oestlund, I., Snoep, J. L., Schiffer, L., Wabitsch, M., Arlt, W., & Storbeck, K. (2023) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2023.106436 · Cited by 10
Park, S. B., Park, J. S., Jung, W. H., Park, A., Jo, S. R., Kim, H. Y., Rhee, S. D., Ryu, S. Y., Jeong, H. G., Park, S., et al. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.10.014 · Cited by 10
Katz, A., Heiblum, R., Meidan, R., & Robinzon, B. (2007) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2007.06.015 · Cited by 10
Expression of hexose-6-phosphate dehydrogenase in rat tissues
Marcolongo, P., Senesi, S., Giunti, R., Csala, M., Fulceri, R., Bánhegyi, G., & Benedetti, A. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.05.006 · Cited by 10
Wang, D.-Y., Lu, Q., Walsh, S. L., Payne, L. A., Modha, S. S., Scott, M. J., Sweitzer, T. D., Ames, R. S., Krosky, D. J., & Li, H. (2008) · Molecular Biotechnology · doi:10.1007/s12033-008-9050-y · Cited by 10
Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary–gonadal axis of primates
Bird, A. D., Greatorex, S., Reser, D. H., Lavery, G. G., & Cole, T. J. (2017) · Endocrine Connections · doi:10.1530/ec-17-0119 · Cited by 9
Quantitation and cellular localization of 11β-HSD1 expression in murine thymus
Nuotio-Antar, A. M., Hasty, A. H., & Kovacs, W. J. (2006) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.01.011 · Cited by 9
Størkson, R. H., Aamodt, R., Vetvik, K. K., Pietiläinen, K. H., Bukholm, G., Jónsdóttir, K., Vollan, H. S., Sonerud, T., Lüders, T., Jacobsen, M., et al. (2012) · International Journal of Colorectal Disease · doi:10.1007/s00384-012-1442-6 · Cited by 10
Reciprocal Changes in Maternal and Fetal Metabolism of Corticosterone in Rat During Gestation
Vagnerová, K., Vacková, Z., Klusoňová, P., Štaud, F., Kopecký, M., Ergang, P., Mikšı́k, I., & Pácha, J. (2008) · Reproductive Sciences · doi:10.1177/1933719108319161 · Cited by 9
Zhu, Q., Dong, Y., Li, X., Ni, C., Huang, T., Sun, J., & Ge, R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00886 · Cited by 7
Effects of free access to sugar solutions on the control of energy intake
Zhao, C., & Castonguay, T. W. (2016) · Food Reviews International · doi:10.1080/87559129.2016.1149863 · Cited by 7
Cellular and genetic models of H6PDH and 11β‐HSD1 function in skeletal muscle
Zielinska, A. E., Fletcher, R. S., Sherlock, M., Doig, C. L., & Lavery, G. G. (2017) · Cell Biochemistry and Function · doi:10.1002/cbf.3272 · Cited by 6
Li, X., Hu, G., Li, X., Wang, Y., Hu, Y., Zhou, H.-Y., Latif, S. A., Morris, D. J., Chu, Y., Zheng, Z., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141767 · Cited by 6
Cabrera-Sharp, V., Mirczuk, S. M., Shervill, E., Michael, A. E., & Fowkes, R. C. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1613-y · Cited by 5
La 11β-hydroxystéroïde déshydrogénase de type 1 – 1 partie
Iovino, A., & Scheen, A. J. (2009) · Médecine des Maladies Métaboliques · doi:10.1016/s1957-2557(09)73299-7 · Cited by 5
C21-steroids inactivation and glucocorticoid synthesis in the developing lung
Boucher, É. L., Provost, P. R., & Tremblay, Y. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.11.025 · Cited by 6
Chandrakesan, P., Sambandam, Y., Ilangovan, R., Janani, P., Palaniyandi, K., Balaganesh, M., Bhaskaran, N., Sittadjody, S., & Balasubramanian, K. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.06.014 · Cited by 3
Porzezińska-Furtak, J., Krzyżanowska‐Świniarska, B., Miazgowski, T., Ziemak, J., & Widecka, K. (2009) · Endokrynologia, Otyłość i Zaburzenia Przemiany Materii · Cited by 3
11β-Hydroxysteroid Dehydrogenases in the Regulation of Tissue Glucocorticoid Availability
Pereira, C., Monteiro, R., Constância, M., & João, M. (2012) · InTech eBooks · doi:10.5772/53645 · Cited by 3
11β-Hydroxysteroid Dehydrogenase Type 1 and the Metabolic Syndrome
Cidalia, D., Maria, J., Azevedo, I., & Monteiro, R. (2011) · InTech eBooks · doi:10.5772/28641 · Cited by 2
Sequence and expression of 11β-hydroxysteroid dehydrogenase type 1 cDNA cloned from pig testis
Ohno, S., Ohta, M., Honda, Y., & Nakajin, S. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0348-2 · Cited by 2
Klusoňová, P., Pátková, L., Ergang, P., Mikšı́k, I., Zicha, J., Kuneš, J., & Pácha, J. (2011) · Steroids · doi:10.1016/j.steroids.2011.06.003 · Cited by 2
[Reduction of obesity-related metabolic risk by modulating tissue exposition to cortisol].
Iovino, A., Paquot, N., & Scheen, A. J. (2010) · PubMed · Cited by 2
Cortisol Metabolism as a Regulator of the Tissue-Specific Glucocorticoid Action
Sbardella, E., & Tomlinson, J. (2016) · Springer eBooks · doi:10.1007/978-3-319-45950-9_14 · Cited by 2
Self-citationMichael, A. E., Thurston, L. M., & Fowkes, R. C. (2019) · Biology · doi:10.3390/biology8040081 · Cited by 2
Iovino, A., Paquot, N., & Scheen, A. J. (2009) · Obésité · doi:10.1007/s11690-009-0204-2 · Cited by 1
Sambuceti, G., Morbelli, S. D., Cossu, V., Marini, C., & Bauckneht, M. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.206797 · Cited by 1
Estrogen and Glucocorticoid Metabolism
Andersson, T. (2010) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Stachoń, M., Fürstenberg, E., Siriska, B., Gadzialska, J., & Gromadzka-Ostrowska, J. (2006) · Polish Journal of Food and Nutrition Sciences
Bos, P. (2010) · Nottingham ePrints (University of Nottingham)
Title of dissertation: HIGH SUCROSE, FRUCTOSE, AND GLUCOSE DIETS AND GLUCOCORTICOID DYSREGULATION IN
London, E., & Castonguay, T. W. (2009)
The impact of glucocorticoids upon the insulin sensitivity of skeletal muscle
Morgan, S. (2010) · University of Birmingham Institutional Research Archive (University of Birmingham)
Alterations in peripheral glucocorticoid metabolism : effects of weight changes
Šimonytė, K. (2011) · DiVA at Umeå University (Umeå University)
Edwards, C. R. W. (2024) · Obstetrics and gynecology. · doi:10.5772/intechopen.1005047
Blaschke, M., Dressel, I., Koepp, R., Armbrecht, G., Sehmisch, S., Tzvetkov, M. V., Streit, F., Reichardt, H. M., Glüer, C., & Siggelkow, H. (2025) · PNAS Nexus · doi:10.1093/pnasnexus/pgaf315
Gjorgoska, M., Pečnik, K., Marolt, N., Plavec, J., & Rižner, T. L. (2026) · Cancer Cell International · doi:10.1186/s12935-026-04453-6
Mineralocorticoid receptor overactivation in heart failure with preserved ejection fraction
Kobayashi, M., Pitt, B., & Zannad, F. M. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehag578
Regulation of the Mineralocorticoid Receptor in Physiology and Disease
Young, M. J., Fuller, P. J., Meijer, O. C., Cole, T. J., Kanki, M., Yang, J., Ho, Q. V., Karthigan, N., & Heanue, S. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100156
Characterisation of 11beta hydroxysteroid dehydrogenase 1 in ocular and orbital tissues
Onyimba, C. (2010) · UPT. Syiah Kuala University Library (Syiah Kuala University)
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review