20 hydroxysteroid dehydrogenases

Summary

Summary: A group of enzymes that catalyze the reversible reduction-oxidation reaction of 20-hydroxysteroids, such as from a 20-ketosteroid to a 20-alpha-hydroxysteroid (EC 1.1.1.149) or to a 20-beta-hydroxysteroid (EC 1.1.1.53).

Top Publications

  1. ncbi Expression, purification and characterization of the rat luteal 20 alpha-hydroxysteroid dehydrogenase
    J Mao
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612 7342, USA
    Endocrinology 138:182-90. 1997
  2. ncbi Prostaglandin F2alpha-induced expression of 20alpha-hydroxysteroid dehydrogenase involves the transcription factor NUR77
    C O Stocco
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, Illinois 60612, USA
    J Biol Chem 275:37202-11. 2000
  3. ncbi Identification of a major prolactin-regulated protein as 20 alpha-hydroxysteroid dehydrogenase: coordinate regulation of its activity, protein content, and messenger ribonucleic acid expression
    C T Albarracin
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612
    Endocrinology 134:2453-60. 1994
  4. ncbi Characterization of a human 20alpha-hydroxysteroid dehydrogenase
    Y Zhang
    Oncology and Molecular Endocrinology Research Center, CHUQ PCHUL and Laval University, Quebec, Quebec G1V 4G2, Canada
    J Mol Endocrinol 25:221-8. 2000
  5. ncbi Luteolytic action of RU486: modulation of luteal 3 beta-hydroxysteroid dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in late pregnant rats
    C M Telleria
    Laboratorio de Reproduccion y Lactancia, CRICYT CONICET, Mendoza, Argentina
    J Steroid Biochem Mol Biol 52:567-73. 1995
  6. ncbi Molecular cloning and characterization of the rat ovarian 20 alpha-hydroxysteroid dehydrogenase gene
    L Zhong
    Department of Physiology and Biophysics, University of Illinois at Chicago 60612, USA
    Biochem Biophys Res Commun 249:797-803. 1998
  7. ncbi Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism
    Qing Ji
    Division of Gastrointestinal and Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    Prostate 54:275-89. 2003
  8. ncbi Isolation and characterization of a rat luteal cDNA encoding 20 alpha-hydroxysteroid dehydrogenase
    J Mao
    Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago 60612
    Biochem Biophys Res Commun 201:1289-95. 1994
  9. ncbi The different forms of the prolactin receptor in the rat corpus luteum: developmental expression and hormonal regulation in pregnancy
    C M Telleria
    Department of Physiology and Biophysics, College of Medicine, University of Illinois, Chicago 60612, USA
    Endocrinology 138:4812-20. 1997
  10. ncbi AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer
    Tea Lanisnik Rizner
    Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 248:126-35. 2006

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Scientific Experts

Detail Information

Publications116 found, 100 shown here

  1. ncbi Expression, purification and characterization of the rat luteal 20 alpha-hydroxysteroid dehydrogenase
    J Mao
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612 7342, USA
    Endocrinology 138:182-90. 1997
    ..e. posttranslational modification of 20 alpha HSD may not be required for the maximal expression of enzyme activity...
  2. ncbi Prostaglandin F2alpha-induced expression of 20alpha-hydroxysteroid dehydrogenase involves the transcription factor NUR77
    C O Stocco
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, Illinois 60612, USA
    J Biol Chem 275:37202-11. 2000
    ....
  3. ncbi Identification of a major prolactin-regulated protein as 20 alpha-hydroxysteroid dehydrogenase: coordinate regulation of its activity, protein content, and messenger ribonucleic acid expression
    C T Albarracin
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612
    Endocrinology 134:2453-60. 1994
    ....
  4. ncbi Characterization of a human 20alpha-hydroxysteroid dehydrogenase
    Y Zhang
    Oncology and Molecular Endocrinology Research Center, CHUQ PCHUL and Laval University, Quebec, Quebec G1V 4G2, Canada
    J Mol Endocrinol 25:221-8. 2000
    ..The present study clearly indicates that the genuine human 20alpha-HSD belongs to the aldoketo reductase family, like the 20alpha-HSDs from other species...
  5. ncbi Luteolytic action of RU486: modulation of luteal 3 beta-hydroxysteroid dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in late pregnant rats
    C M Telleria
    Laboratorio de Reproduccion y Lactancia, CRICYT CONICET, Mendoza, Argentina
    J Steroid Biochem Mol Biol 52:567-73. 1995
    ..Prostaglandins seems to be involved in the increase of 20 alpha-HSD activity and therefore, in the demise of corpora lutea...
  6. ncbi Molecular cloning and characterization of the rat ovarian 20 alpha-hydroxysteroid dehydrogenase gene
    L Zhong
    Department of Physiology and Biophysics, University of Illinois at Chicago 60612, USA
    Biochem Biophys Res Commun 249:797-803. 1998
    ..In summary, we have identified and partially characterized the promoter region of the rat ovarian 20 alpha-HSD and demonstrated that the regulatory elements for 20 alpha-HSD are present within a 2.5 kb 5' flanking region of the gene...
  7. ncbi Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism
    Qing Ji
    Division of Gastrointestinal and Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    Prostate 54:275-89. 2003
    ..Functional activity and regulation of AKR1C2, a 3 alpha-hydroxysteroid dehydrogenase (HSD) type III, was also assessed in prostate cancer cell lines...
  8. ncbi Isolation and characterization of a rat luteal cDNA encoding 20 alpha-hydroxysteroid dehydrogenase
    J Mao
    Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago 60612
    Biochem Biophys Res Commun 201:1289-95. 1994
    ..Prolactin reduced markedly 20 alpha HSD mRNA expression. No signal was detected in other tissues examined, demonstrating the specific expression of this enzyme in the corpus luteum...
  9. ncbi The different forms of the prolactin receptor in the rat corpus luteum: developmental expression and hormonal regulation in pregnancy
    C M Telleria
    Department of Physiology and Biophysics, College of Medicine, University of Illinois, Chicago 60612, USA
    Endocrinology 138:4812-20. 1997
    ....
  10. ncbi AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer
    Tea Lanisnik Rizner
    Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 248:126-35. 2006
    ..It is suggested that the expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2...
  11. ncbi Prostaglandin F(2alpha) (PGF(2alpha)) and prolactin signaling: PGF(2alpha)-mediated inhibition of prolactin receptor expression in the Corpus luteum
    Carlos Stocco
    Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    Endocrinology 144:3301-5. 2003
    ..The results further suggest that PGF(2alpha)-mediated stimulation of 20alphaHSD is independent from PGF(2alpha) inhibition of PRL signaling in luteal cell...
  12. ncbi Cytosolic 20 alpha-hydroxysteroid dehydrogenase activity in spontaneous neoplasms in the dog and cat
    K Shiota
    Laboratory of Cellular Biochemistry, Veterinary Medical Science, University of Tokyo, Japan
    J Vet Med Sci 53:549-52. 1991
    ..Furthermore, 20 alpha-HSD activity in the cytosol fraction from malignant tumours was increased dramatically by passage through the DEAE column, suggesting that the enzyme is present in the cytosol as an inactive or sequestered form...
  13. ncbi 20 alpha-hydroxysteroid dehydrogenase activity in canine spontaneous neoplasms
    N M Tanaka
    Department of Veterinary Surgery, University of Tokyo, Japan
    J Vet Med Sci 56:581-3. 1994
    ..Thus, 20 alpha-HSD activity was found in neoplastic tissues at a considerable high rate and the activity seemed to be higher in pathologically malignant tumors...
  14. ncbi Dual regulation of luteal progesterone production by androstenedione during spontaneous and RU486-induced luteolysis in pregnant rats
    C M Telleria
    Laboratorio de Reproduccion y Lactancia, CRICYT CONICET, Mendoza, Argentina
    J Steroid Biochem Mol Biol 55:385-93. 1995
    ....
  15. ncbi Tibolone is metabolized by the 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four human isozymes of the aldo-keto reductase 1C subfamily: inversion of stereospecificity with a delta5(10)-3-ketosteroid
    Stephan Steckelbroeck
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    Mol Pharmacol 66:1702-11. 2004
    ....
  16. ncbi Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling
    Qing Ji
    Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    Cancer Res 64:7610-7. 2004
    ..We speculate that loss of AKR1C1 and AKR1C2 in breast cancer results in decreased progesterone catabolism, which, in combination with increased PR expression, may augment progesterone signaling by its nuclear receptors...
  17. pmc Luteal 3beta-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities in the rat corpus luteum of pseudopregnancy: effect of the deciduoma reaction
    Marisa A Clementi
    Laboratorio de Reproduccion y Lactancia, IMBECU CONICET, Mendoza, Argentina
    Reprod Biol Endocrinol 2:22. 2004
    ....
  18. ncbi Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes
    M Nishizawa
    Department of Medical Chemistry Department of Obstetrics and Gynecology, Kansai Medical University, 10 15 Fumizono, Moriguchi, Osaka 570 8506, Japan
    Genes Cells 5:111-25. 2000
    ..High homology between human 20alpha-HSD [AKR 1C1] cDNA with other AKRs had caused difficulty in gene isolation and expression analysis. Thus, the metabolism of progesterone in the human reproductive system remained unclear...
  19. ncbi Changes in mRNAs encoding steroidogenic acute regulatory protein, steroidogenic enzymes and receptors for gonadotropins during spermatogenesis in rainbow trout testes
    M Kusakabe
    School of Aquatic and Fishery Sciences, University of Washington, 1140 Boat Street NE, Seattle, Washington 98195 5020, USA
    J Endocrinol 189:541-54. 2006
    ....
  20. ncbi Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids
    Jean Francois Couture
    Oncology and Molecular Endocrinology Research Center, Laval University Medical Center CHUL 2705 boul Laurier, Ste Foy, QC, Canada G1V 4G2
    J Mol Biol 331:593-604. 2003
    ..We thus propose that Prog is maintained in a new steroid-binding site composed mainly of residues found in the carboxy-terminal region of the protein...
  21. ncbi Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1
    Petra Brozic
    Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 259:30-42. 2006
    ..Docking of the flavones in the active site of AKR1C1 revealed their possible binding modes, in which they are sandwiched between the Leu308 and Trp227 of AKR1C1...
  22. ncbi Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity
    L Wu
    Departments of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065
    J Biol Chem 268:12964-9. 1993
    ..The amount of 17 beta-HSD type 2 mRNA in placenta was found to be high. The data suggest that the 17 beta-HSD type 2 cDNA encodes the microsomal 17 beta-HSD of human placenta, described by several laboratories...
  23. ncbi Impaired dihydrotestosterone catabolism in human prostate cancer: critical role of AKR1C2 as a pre-receptor regulator of androgen receptor signaling
    Qing Ji
    Department of Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Cancer Res 67:1361-9. 2007
    ..We speculate that selective loss of AKR1C2 in prostate cancer promotes clonal expansion of tumor cells by enhancement of androgen-dependent cellular proliferation by reducing DHT metabolism...
  24. ncbi Cadmium, cobalt and lead cause stress response, cell cycle deregulation and increased steroid as well as xenobiotic metabolism in primary normal human bronchial epithelial cells which is coordinated by at least nine transcription factors
    Felix Glahn
    Institute of Environmental Toxicology, Martin Luther University, Halle Wittenberg, Halle Saale, Germany
    Arch Toxicol 82:513-24. 2008
    ..This study gives an overview of the most responsive genes...
  25. ncbi Molecular cloning of testicular 20 alpha-hydroxysteroid dehydrogenase: identity with aldose reductase
    J C Warren
    Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri 63110
    Biochemistry 32:1401-6. 1993
    ..Because aldose reductase has been implicated in the etiology of diabetic complications, acceptance of steroid substrates may offer new implications for therapy...
  26. ncbi Human chorionic gonadotropin-dependent induction of an equine aldo-keto reductase (AKR1C23) with 20alpha-hydroxysteroid dehydrogenase activity during follicular luteinization in vivo
    K A Brown
    Centre de recherche en reproduction animale et Département de biomédecine vétérinaire, Faculte de Medecine Veterinaire, Universite de Montreal, Quebec, Canada J2S 7C6
    J Mol Endocrinol 36:449-61. 2006
    ..The nucleotide sequence reported in this paper has been submitted to GenBank with accession number AY955082.)...
  27. ncbi Cloning and expression of chicken 20-hydroxysteroid dehydrogenase
    J Bryndová
    Institute of Physiology, Czech Academy of Sciences, Videnska 1083, CZ 142 20 Prague 4 Krc, Czech Republic
    J Mol Endocrinol 37:453-62. 2006
    ..These results suggest that chicken 20HSD is the latest member of the SDR superfamily to be found, is expressed in many avian tissues and whose precise role remains to be determined...
  28. ncbi 3alpha/beta,20beta-hydroxysteroid dehydrogenase (porcine testicular carbonyl reductase) also has a cysteine residue that is involved in binding of cofactor NADPH
    Takuya Sugiyama
    Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2 4 41, Ebara, Shinagawa ku, Tokyo 142 8501, Japan
    J Steroid Biochem Mol Biol 88:393-8. 2004
    ..On the basis of the tertiary structure of 3alpha/beta,20beta-HSD, the possible roles of Cys residues, especially that of Cys 226, in enzyme action and in the binding of cofactor NADPH are discussed...
  29. pmc Iodine alters gene expression in the MCF7 breast cancer cell line: evidence for an anti-estrogen effect of iodine
    Frederick R Stoddard
    Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA
    Int J Med Sci 5:189-96. 2008
    ....
  30. ncbi Hypothyroidism prolongs corpus luteum function in the pregnant rat
    María Belén Hapon
    Laboratorio de Reproduccion y Lactancia, IMBECU CONICET, Mendoza, Argentina
    Reproduction 133:197-205. 2007
    ....
  31. ncbi Neonatal superior ovarian nerve transection disturbs the cyclic activity of the female rats
    Myriam L Forneris
    Laboratorio de Biología de la Reproducción LABIR, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, Argentina
    J Steroid Biochem Mol Biol 82:75-82. 2002
    ..The functional changes observed in the ovary suggest a possible alteration in the hypothalamic-hypophyseal axis...
  32. ncbi Enantioselectivity of carbonyl reduction of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone by tissue fractions from human and rat and by enzymes isolated from human liver
    Ursula Breyer-Pfaff
    Department of Pharmacology and Toxicology, University of Tubingen, Germany
    Drug Metab Dispos 32:915-22. 2004
    ..Rat liver and lung microsomes produced NNAL with about 33% and 55% (R)-enantiomer and a mean contribution of 11beta-HSD1 of 12% and 32%, respectively. Multiple enzymes seem to participate in NNK reduction in human and rat tissues...
  33. ncbi [Effect of DRB/alpha-Amanitin on localization of Nrf2 in A549 cells]
    Li Yan Qu
    Department of Biochemistry and Genetics, College of Medicine, Zhejiang University, Hangzhou, China
    Zhejiang Da Xue Xue Bao Yi Xue Ban 39:24-9. 2010
    ..To investigate the effects of transcriptional inhibitors 5, 6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) and alpha-Amanitin on the localization of Nrf2 in the nucleus...
  34. ncbi Factorizing the role of a critical leucine residue in the binding of substrate to human 20alpha-hydroxysteroid dehydrogenase (AKR1C1): molecular modeling and kinetic studies of the Leu308Val mutant enzyme
    Urmi Dhagat
    Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia
    Bioorg Med Chem Lett 20:5274-6. 2010
    ....
  35. ncbi Expression of steroid-converting enzymes in osteoblasts derived from rat vertebrae
    Y Ishida
    Faculty of Dentistry, University of Toronto, Ontario, Canada
    Osteoporos Int 13:235-40. 2002
    ....
  36. ncbi Expression of ovarian 20alpha-hydroxysteroid dehydrogenase in rat thymus
    K Hirabayashi
    Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo, Japan
    Endocr J 48:557-63. 2001
    ..These results suggest that the same molecular species as ovarian 20a-HSD is expressed in thymic lymphocytes. Therefore, 20alpha-HSD may play a role in T-lymphocyte proliferation and differentiation processes...
  37. ncbi Expression, crystallization and preliminary X-ray analysis of human and rabbit 20alpha-hydroxysteroid dehydrogenases in complex with NADP(H) and various steroid substrates
    Jean Francois Couture
    Oncology and Molecular Endocrinology Research Center, Laval University Medical Center CHUL and Laval University, Quebec G1V 4G2, Canada
    Acta Crystallogr D Biol Crystallogr 58:135-9. 2002
    ..7 A) or 4-androstenedione (1.8 A). All these crystals belong to the monoclinic space group P2(1). A partial data set has also been collected for a crystal of h20alpha-HSD (P2(1)2(1)2(1)) in complex with NADP(H) and progesterone...
  38. ncbi New cyclopentane derivatives as inhibitors of steroid metabolizing enzymes AKR1C1 and AKR1C3
    Bogdan Stefane
    Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, 1000 Ljubljana, Slovenia
    Eur J Med Chem 44:2563-71. 2009
    ..These compounds represent promising starting points in the development of new anticancer agents for the treatment of hormone-dependent forms of cancer and other diseases where AKR1C1 and AKR1C3 are involved...
  39. ncbi Androgen metabolism in adipose tissue: recent advances
    Karine Blouin
    Molecular Endocrinology and Oncology Research Center, Laval University Medical Research Center, Canada Department of Nutrition, Laval University, Canada
    Mol Cell Endocrinol 301:97-103. 2009
    ..We hypothesize that body fat distribution patterns likely emerge from the local adipose tissue balance between active androgens and glucocorticoids in each fat compartment...
  40. ncbi Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer
    David R Bauman
    Department of Pharmacology, Center of Excellence in Environmental Toxicology, University of Pennsylvania School of Medicine, 130C John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104 6084, USA
    Endocrinology 147:5806-16. 2006
    ..280 in normal PSC) were maintained in PEC and PSC in diseased prostate. These data suggest that CaP may be more responsive to an ERbeta agonist and BPH may be more responsive to androgen ablation...
  41. ncbi Metabolic enzyme induction by HepG2 cells exposed to oxygenated and nonoxygenated polycyclic aromatic hydrocarbons
    Kentaro Misaki
    Department of Environmental Engineering and Graduate School of Global Environmental Studies, Kyoto University, Yoshidahonmachi, Kyoto 606 8501, Japan
    Chem Res Toxicol 20:277-83. 2007
    ..Both chemical-dependent and time-dependent induction patterns of NQO1 mRNA were of the mixed types of P4501A1 and AKR1C1. The tendency for the decrease of GSTM1 mRNA was observed when exposed to PAHs B[a]P and B[k]FA...
  42. ncbi Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women
    Karine Blouin
    Molecular Endocrinology and Oncology Research Center, Dept of Nutrition, Laval University Medical Center, 2705 Laurier Boulevard, Rm T3 67, Quebec City, Prov Quebec, Canada G1V 4G2
    Am J Physiol Endocrinol Metab 288:E398-404. 2005
    ..Increased progesterone and/or dihydrotestosterone reduction in abdominal adipose tissue may impact locally on fat cell metabolism...
  43. ncbi Progesterone metabolism in adipose cells
    Yonghua Zhang
    Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Quebec City, Canada
    Mol Cell Endocrinol 298:76-83. 2009
    ..In conclusion, preadipocytes and lipid-storing, mature adipocytes efficiently generate progesterone metabolites in women, which is consistent with rather modest effects progesterone on abdominal fat cell differentiation...
  44. pmc Effects of tibolone metabolites on human endometrial cell lines in co-culture
    Claire Barbier
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599 7525, USA
    Reprod Sci 15:75-82. 2008
    ..Thus, the unexpected progestagenic effect of 3beta-OH-tibolone in these co-cultures may be due to metabolic activity present in the stromal cells of the co-cultures...
  45. pmc Estrogen and progesterone metabolism in the cervix during pregnancy and parturition
    Stefan Andersson
    Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9032, USA
    J Clin Endocrinol Metab 93:2366-74. 2008
    ..Mice deficient in 5alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood...
  46. ncbi Crystal structure of human prostaglandin F synthase (AKR1C3)
    Junichi Komoto
    Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045 7534, USA
    Biochemistry 43:2188-98. 2004
    ..Since the substrate binding cavity of PGFS is relatively large in comparison with those of AKR1C1 and AKR1C2, PGFS (AKR1C3) could catalyze the reduction and/or oxidation reactions of various compounds over a relatively wide pH range...
  47. ncbi Structure-function relationships in 3alpha-hydroxysteroid dehydrogenases: a comparison of the rat and human isoforms
    Trevor M Penning
    Department of Pharmacology, School of Medicine, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    J Steroid Biochem Mol Biol 85:247-55. 2003
    ..Instead the low k(cat) seen in AKR1C2 (50-fold less than AKR1C9) may be due to substrate "wobble" at the plastic active site...
  48. ncbi Aberrant pre-receptor regulation of estrogen and progesterone action in endometrial cancer
    Tina Smuc
    Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 301:74-82. 2009
    ..Up-regulation of AKR1C1 and AKR1C3 can result in lower levels of the protective progesterone, which acts mainly via PR-B...
  49. ncbi Dependence on prolactin of the luteolytic effect of prostaglandin F2alpha in rat luteal cell cultures
    A Zetser
    Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa 31096, Israel
    Biol Reprod 65:1082-91. 2001
    ....
  50. ncbi Participation of intraluteal progesterone and prostaglandin F2 alpha in LH-induced luteolysis in pregnant rat
    C O Stocco
    , CRICYT CONICET, Mendoza, Argentina
    J Endocrinol 156:253-9. 1998
    ..Thus, the early decline in 3 beta-HSD activity and the consequent fall in intraluteal P4 content, may trigger the synthesis of PGs and thereafter the increase in luteal 20 alpha-HSD activity to establish luteolysis...
  51. ncbi Prolactin-mediated inhibition of 20alpha-hydroxysteroid dehydrogenase gene expression and the tyrosine kinase system
    L Zhong
    Department of Physiology and Biophysics, University of Illinois at Chicago, 60612, USA
    Biochem Biophys Res Commun 235:587-92. 1997
    ....
  52. ncbi Synthesis of 20 alpha-hydroxylated steroids by ovaries of the dab (Limanda limanda)
    A V Canario
    Universidade do Algarve, Faro, Portugal
    Gen Comp Endocrinol 76:147-58. 1989
    ..High concentrations of both 17,20 alpha-P and 3 beta,17,20 alpha-P-5 beta found in female and male dab plasma. The possible role of these steroids is discussed...
  53. ncbi The 20 alpha-hydroxysteroid dehydrogenase of Streptomyces hydrogenans
    R L Rimsay
    Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St John s, Canada
    Eur J Biochem 174:437-42. 1988
    ..This enzyme catalyzes the transfer of hydrogen from the 4-pro-S position of NADH...
  54. ncbi Prostaglandin-E2 9-reductase from corpus luteum of pseudopregnant rabbit is a member of the aldo-keto reductase superfamily featuring 20 alpha-hydroxysteroid dehydrogenase activity
    N Wintergalen
    Zentrum für Frauenheilkunde, Westfalische Wilhelms Universitat, Munster, Germany
    Eur J Biochem 234:264-70. 1995
    ..For this reason the aldo-keto reductase could be a key enzyme in the cascade of events leading to the regression of the corpus luteum in the rabbit...
  55. ncbi Progesterone receptor is not required for progesterone action in the rat corpus luteum of pregnancy
    C M Telleria
    Laboratorio de Reproduccion y Lactancia, from Consejo Nacional de Investigaciones Científicas y Técnicas, Mendoza, Argentina
    Steroids 64:760-6. 1999
    ..In summary, this report provides further evidence of a local action of progesterone regulating luteal function in the rat despite the absence of a classic PR...
  56. ncbi Denaturation by urea and renaturation of 20 beta-hydroxysteroid dehydrogenase studied by high-performance size exclusion chromatography
    G Carrea
    Istituto di Chimica degli Ormoni del C N R, Milan, Italy
    Anal Biochem 180:181-5. 1989
    ..The contemporaneous measurement of recovery of activity unambiguously demonstrated that the tetrameric structure is essential for enzymatic activity...
  57. ncbi [Physiological, genetic and pathological factors regulating the reductive metabolism of drugs with a ketone group]
    Y Imamura
    Faculty of Pharmaceutical Sciences, Kumamoto University, Japan
    Yakugaku Zasshi 119:835-49. 1999
    ..We propose the possibility that the male-specific microsomal enzyme physiologically functions as a 20 beta-hydroxysteroid dehydrogenase...
  58. ncbi The reactive oxygen species--and Michael acceptor-inducible human aldo-keto reductase AKR1C1 reduces the alpha,beta-unsaturated aldehyde 4-hydroxy-2-nonenal to 1,4-dihydroxy-2-nonene
    M E Burczynski
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA
    J Biol Chem 276:2890-7. 2001
    ..AKRs represent alternative GSH-independent/NADPH-dependent routes for the reductive elimination of HNE. Of these, AKR1C1 provides an inducible cytosolic barrier to HNE following ROS exposure...
  59. ncbi Expression of genes involved in prostaglandin E2 and progesterone production in bovine cumulus-oocyte complexes during in vitro maturation and fertilization
    Fabienne Nuttinck
    ENVA, UMR 1198, Biologie du Developpement et Reproduction, 7 av du Général De Gaulle, Maisons Alfort F 94704, France
    Reproduction 135:593-603. 2008
    ....
  60. ncbi Steroidogenic enzyme activities in rat polycystic ovaries
    G M Cooke
    Departement d anatomie et physiologie animale, , St Hyacinthe, PQ, Canada
    Can J Physiol Pharmacol 71:247-53. 1993
    ..Lyase and aromatase activities were undetectable in cystic ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)..
  61. ncbi Engineering steroid hormone specificity into aldo-keto reductases
    T M Penning
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 19104 6084, Philadelphia, PA, USA
    Chem Biol Interact 130:659-71. 2001
    ..Protein engineering with predicted outcomes demonstrates that the molecular determinants of steroid hormone recognition in AKRs will be ultimately rationalized...
  62. ncbi Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin
    Hao Wei Wang
    Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan
    Int J Cancer 120:2019-27. 2007
    ..Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression...
  63. ncbi Effect of calyculin-A, phosphatase inhibitor, on 20 alpha-hydroxysteroid dehydrogenase activity in rat luteal cell culture
    K Yamanouchi
    Department of Veterinary Physiology, Veterinary Medical Science, University of Tokyo, Japan
    Endocr J 40:699-704. 1993
    ..These results suggest that a CL-A sensitive phosphatase(s) may be involved in the action of PRL in suppressing the increase in 20 alpha-HSD activity in rat luteal cells...
  64. pmc Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha
    Xiu Jun Wang
    Cancer Research U K Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom
    Proc Natl Acad Sci U S A 104:19589-94. 2007
    ..These data suggest that cross-talk between Nrf2 and RARalpha could markedly influence the sensitivity of cells to electrophiles and oxidative stressors and, as a consequence, to carcinogenesis...
  65. ncbi Transcriptional regulation of aldo-keto reductase 1C1 in HT29 human colon cancer cells resistant to methotrexate: role in the cell cycle and apoptosis
    Elisabet Selga
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av Diagonal 643, E 08028 Barcelona, Spain
    Biochem Pharmacol 75:414-26. 2008
    ..Finally, overexpression of AKR1C1 in MTX sensitive HT29 cells conferred resistance to the chemotherapeutic agent and silencing of AKR1C1 by means of iRNA technology sensitized the cells to MTX...
  66. pmc Metabolism of benzo[a]pyrene in human bronchoalveolar H358 cells using liquid chromatography-mass spectrometry
    Hao Jiang
    Centers of Excellence in Environmental Toxicology and Cancer Pharmacology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Chem Res Toxicol 20:1331-41. 2007
    ..It also provides evidence that each of the pathways of PAH activation yields their distinctive metabolites in H358 human lung cells and that each pathway may contribute to the carcinogenic process...
  67. ncbi Aldo-keto reductases (AKR) from the AKR1C subfamily catalyze the carbonyl reduction of the novel anticancer drug oracin in man
    Vladimir Wsol
    Faculty of Pharmacy, Charles University, Heyrovskeho 1203, CZ 50005 Hradec Kralove, Czech Republic
    Toxicology 238:111-8. 2007
    ..Detailed knowledge about all enzymes involved in oracin detoxification may help to improve an anticancer regimen by co-application of respective inhibitors...
  68. ncbi 20 alpha-Hydroxysteroid dehydrogenase activity in rat placenta
    K Shiota
    Laboratory of Cellular Biochemistry, University of Tokyo, Japan
    Endocr J 40:673-81. 1993
    ..The number of fetuses on day 10 of pregnancy was 15.4 and decreased significantly to 12.9 on day 12.(ABSTRACT TRUNCATED AT 250 WORDS)..
  69. ncbi Molecular characterization of the cynomolgus monkey Macaca fascicularis steroidogenic enzymes belonging to the aldo-keto reductase family
    Hong Liu
    Oncology and Molecular Endocrinology Research Center, Laval University Medical Center CRCHUL and Laval University, 2705 Laurier Boulevard, Quebec G1V 4G2, Canada
    J Steroid Biochem Mol Biol 104:75-80. 2007
    ..Monkey 20alpha-HSD mRNA is highly expressed in the kidney, stomach, and liver. Our study provides the basis for future investigations on the regulation and function of these enzymes in the monkey...
  70. ncbi Expression of activities of two 20 alpha-hydroxysteroid dehydrogenase isozymes in rat corpora lutea
    H H Seong
    Department of Veterinary Physiology, University of Tokyo, Japan
    J Reprod Fertil 96:573-80. 1992
    ..Thus, the increase in total enzyme activity and appearance of HSD-2 activity observed at late pseudopregnancy was accompanied by an increase in the number of 20 alpha-HSD-positive luteal cells...
  71. ncbi Steroid C-20 oxidoreductase activity of duck intestinal mucosa: the interrelations of the enzymatic activity with steroid binding
    J A DiBattista
    Hôpital Notre Dame et Département de Médecine, Universite de Montreal, Quebec, Canada
    Gen Comp Endocrinol 74:136-47. 1989
    ....
  72. ncbi Inhibition of induction of 20 alpha-hydroxysteroid dehydrogenase activity in rat corpora lutea in vitro by the progesterone antagonist RU486
    J T Uilenbroek
    Department of Endocrinology and Reproduction, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands
    Life Sci 50:1173-8. 1992
    ..However, since these effects in vitro can only be obtained with high concentrations of RU486, it is unlikely that this antiluteolytic effect plays a role after injection of RU486 in vivo...
  73. pmc The CCAAT box binding transcription factor, nuclear factor-Y (NF-Y) regulates transcription of human aldo-keto reductase 1C1 (AKR1C1) gene
    Rajash Pallai
    Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Gene 459:11-23. 2010
    ..These results indicate that the NF-Y regulates the basal transcription of AKR1C1 in human ovarian, lung and liver carcinoma cells and the cisplatin-induced transcription in human ovarian carcinoma cells...
  74. ncbi Ontogeny of testicular steroid dehydrogenase enzymes in pig (3 alpha/beta-, 20 alpha- and 20 beta-): evidence for two forms of 3 alpha/beta-hydroxysteroid dehydrogenase
    S Ohno
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan
    J Steroid Biochem Mol Biol 42:17-21. 1992
    ..The possible functional significance of these changes is considered...
  75. pmc Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds
    A Kenneth MacLeod
    Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Carcinogenesis 30:1571-80. 2009
    ..This study also shows that AKR1B10, AKR1C1 and AKR1C2 proteins have potential utility as biomarkers for NRF2 activation in the human...
  76. ncbi New evidences for the involvement of 20beta-hydroxysteroid dehydrogenase in final oocyte maturation of air-breathing catfish
    G Sreenivasulu
    Department of Animal Sciences, School of Life Sciences, University of Hyderabad, P O Central University, Hyderabad 500 046, Andhra Pradesh, India
    Gen Comp Endocrinol 163:259-69. 2009
    ..These results together provide new evidences for the involvement of 20beta-HSD in the FOM/meiotic maturation...
  77. ncbi [Purification and some properties of 3 alpha-hydroxysteroid dehydrogenase from pig adrenal cytosol]
    S Nakajin
    Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan
    Yakugaku Zasshi 111:775-82. 1991
    ..These results strongly suggest that 3 alpha-HSD purified from pig adrenal cytosol is a bi-functional enzyme catalyzing 3 alpha- and 20 alpha-HSD activities...
  78. ncbi Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes
    Hans Jörg Martin
    Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig Holstein, Campus Kiel, Kiel, Germany
    Chem Biol Interact 178:145-50. 2009
    ..While the best substrates for AKR1B10 are retinals, the high catalytic efficiency together with the protection from inactivation by NADPH suggests a role of AKR1B10 in the detoxification of biogenic aldehydes...
  79. ncbi Derivatives of pyrimidine, phthalimide and anthranilic acid as inhibitors of human hydroxysteroid dehydrogenase AKR1C1
    P Brozic
    Faculty of Medicine, Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia
    Chem Biol Interact 178:158-64. 2009
    ....
  80. ncbi Enzyme kinetics in reversed micelles. 3. Behaviour of 20 beta-hydroxysteroid dehydrogenase
    B Tyrakowska
    Department of Biochemistry, Agricultural University, Wageningen, The Netherlands
    Eur J Biochem 187:81-8. 1990
    ....
  81. pmc Purification and characterization of a novel form of 20 alpha-hydroxysteroid dehydrogenase from Clostridium scindens
    A E Krafft
    Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298 0678
    J Bacteriol 171:2925-32. 1989
    ..The amino-terminal sequence was determined to be Ala-Val-Lys-Val-Ala-Ile-Asn-Gly-Phe-Gly-Arg. These results indicate that this enzyme is a novel form of 20 alpha-hydroxysteroid dehydrogenase...
  82. ncbi Induction of rat granulosa cell steroidogenic enzyme activities and their messenger ribonucleic acids by a splenocyte-derived factor
    J M Ness
    Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242
    Mol Cell Endocrinol 106:163-70. 1994
    ..abstract truncated at 250 words)..
  83. pmc Two pathways for prostaglandin F2 alpha synthesis by the primate periovulatory follicle
    Brandy L Dozier
    Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, Virginia 23507, USA
    Reproduction 136:53-63. 2008
    ..Both of these enzyme activities are present in periovulatory granulosa cells. These data support the concept that follicular PGF2 alpha can be synthesized via two pathways during the periovulatory interval...
  84. pmc Molecular cloning of cDNA for rat ovarian 20 alpha-hydroxysteroid dehydrogenase (HSD1)
    R Miura
    Laboratory of Cellular Biochemistry, University of Tokyo, Japan
    Biochem J 299:561-7. 1994
    ....
  85. ncbi Molecular cloning and expression of an abundant rabbit ovarian protein with 20 alpha-hydroxysteroid dehydrogenase activity
    W Lacy
    Mol Endocrinol 7:1239. 1993
  86. ncbi Progesterone inhibits 20alpha-hydroxysteroid dehydrogenase expression in the rat corpus luteum through the glucocorticoid receptor
    N Sugino
    Department of Physiology and Biophysics, University of Illinois at Chicago, 60612 7342, USA
    Endocrinology 138:4497-500. 1997
    ....
  87. ncbi Characterization of the oxidative 3alpha-hydroxysteroid dehydrogenase activity of human recombinant 11-cis-retinol dehydrogenase
    X F Huang
    Oncology and Molecular Endocrinology Research Center, Laval University Hospital Center (CHUL) and Laval University, 2705 Laurier Boulevard, G1V 4G2, Sainte-Foy, QC, Canada
    Biochim Biophys Acta 1547:351-8. 2001
    ..Taken together, our results suggest that, in humans, this enzyme might play a role in the biosynthesis of both 9-cis-retinoic acid and dihydrotestosterone...
  88. pmc Conversion of mammalian 3alpha-hydroxysteroid dehydrogenase to 20alpha-hydroxysteroid dehydrogenase using loop chimeras: changing specificity from androgens to progestins
    H Ma
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Proc Natl Acad Sci U S A 96:11161-6. 1999
    ..This study represents an example where sex hormone specificity can be changed at the enzyme level...
  89. ncbi Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone
    Yu Higaki
    Laboratory of Biochemistry, Gifu Pharmaceutical University, 5 6 1 Mitahora Higashi, 502 8585, Gifu, Japan
    Chem Biol Interact 143:503-13. 2003
    ..7 nM) in the ordered bi-bi pathway, including an isomerization step. The inhibitors effectively also decreased the reduction of 3alpha,5alpha-THP to its 20alpha-hydroxy metabolite in HepG2 cells treated with ethacrynic acid...
  90. ncbi Luteolytic effects of DL111-IT in pregnant rats
    Y Bo
    Shanghai Institute of Material Medica, China
    Eur J Pharmacol 380:145-52. 1999
    ....
  91. ncbi Progesterone metabolism in human leukemic monoblast U937 cells
    Takashi Suzuki
    Department of Pathology, Tohoku University School of Medicine, Sendai 980 8575, Japan
    Endocr J 49:539-46. 2002
    ..Therefore, our present data suggest that 20alpha-HSD plays an important role in the regulation of progesterone actions in human immune cells...
  92. ncbi Expression of the progesterone receptor and progesterone- metabolising enzymes in the female and male human kidney
    C Bumke-Vogt
    Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universitat Berlin, Germany
    J Endocrinol 175:349-64. 2002
    ..Therefore metabolism of progesterone and/or binding to hPR could reduce competition with aldosterone at the MR and enable the mineralocorticoid function...
  93. ncbi Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung carcinoma (A549) cells
    Nisha T Palackal
    Departments of Biochemistry and Biophysics and Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:24799-808. 2002
    ..The ability to measure DMBA-3,4-dione formation in A549 cells implicates the AKR pathway in the metabolic activation of PAH in human lung...
  94. ncbi Type 5 17beta-hydroxysteroid dehydrogenase: its role in the formation of androgens in women
    V Luu-The
    Medical Research Council Group in Molecular Endocrinology, Oncology and Molecular Endocrinology Research Center, Laval University Hospital CHUL and Laval University, 2705 Laurier Boulevard, G1V 4G2, Quebec, Canada
    Mol Cell Endocrinol 171:77-82. 2001
    ..The double activity of type 5 17beta-HSD in the female reproductive tissues is probably necessary to the control of the optimal level of progesterone and sex steroids...
  95. ncbi [Strain-, sex- and species-related differences of acetohexamide reductase and 20 beta-hydroxysteroid dehydrogenase activities in liver microsomes of experimental animals]
    Y Imamura
    Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto 862-0973, Japan
    Yakugaku Zasshi 121:85-91. 2001
    ....
  96. ncbi The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome
    V L Nelson
    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Clin Endocrinol Metab 86:5925-33. 2001
    ....
  97. ncbi A calcium/calmodulin-dependent activation of ERK1/2 mediates JunD phosphorylation and induction of nur77 and 20alpha-hsd genes by prostaglandin F2alpha in ovarian cells
    Carlos O Stocco
    Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, Illinois 60612, USA
    J Biol Chem 277:3293-302. 2002
    ..We conclude that activation of JunD through a calmodulim-dependent activation of ERK1/2 mediates nur77 induction by PGF(2alpha). Finally, we demonstrated that this molecular mechanism also mediates 20alpha-hsd induction...
  98. pmc Sex-related expression of 20alpha-hydroxysteroid dehydrogenase mRNA in the adult mouse
    G Pelletier
    Oncology and Molecular Endocrinology Research Center, Laval University Medical Center CHUL and Laval University, 2705 Laurier Boulevard, Québec PQ G1V 4G2, Canada
    J Histochem Cytochem 51:1425-36. 2003
    ....
  99. ncbi Expression of 17beta-hydroxysteroid dehydrogenase type 1 and type 2, P450 aromatase, and 20alpha-hydroxysteroid dehydrogenase enzymes in immature, mature, and pregnant rats
    L A Akinola
    Biocenter Oulu and the Department of Clinical Chemistry, University of Oulu, Finland
    Endocrinology 138:2886-92. 1997
    ..The relatively constitutive expression of the enzyme at all physiological stages of the animals suggests a general role for the enzyme in the inactivation of circulating sex steroids...
  100. pmc High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol
    J B Thoden
    Institute for Enzyme Research, Graduate School, University of Wisconsin, Madison 53705, USA
    Protein Sci 5:2149-61. 1996
    ....
  101. ncbi Molecular cloning and expression of an abundant rabbit ovarian protein with 20 alpha-hydroxysteroid dehydrogenase activity
    W R Lacy
    Department of Cell Biology, Baylor College of Medicine Houston, Texas 77030
    Mol Endocrinol 7:58-66. 1993
    ..This is the first example of an abundant crystallin-related protein with known enzymatic activity in a tissue other than the lens...

Research Grants2

  1. Symposium on Aldo-Keto Reductases & Toxicant Metabolism
    TREVOR PENNING; Fiscal Year: 2002
    ..abstract_text> ..
  2. Molecular Mechanisms of Multistage Carcinogenesis
    TREVOR PENNING; Fiscal Year: 2006
    ..By studying the discrete molecular events responsible for the causation of cancer this Program may lead to the early prevention and intervention of this disease. ..