The glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 has broad substrate specificity: Physiological and toxicological considerations

Journal of Steroid Biochemistry and Molecular Biology

Volumn 119, Issue 1-2, 2010, Pages 1-13

  Odermatt, Alex ^a   Nashev, Lyubomir G ^a  

^a Swiss Centre for Applied Human Toxicology   (Switzerland)

Author keywords

11 Hydroxysteroid dehydrogenase; 7 Ketocholesterol; Carbonyl reductase; Detoxification; Glucocorticoid; Hexose 6 phosphate dehydrogenase; Steroid metabolism

Indexed keywords

11 BETA HYDROXYSTEROID; 11 KETOSTEROID; 11 OXYSTEROID; 11BETA HYDROXYSTEROID DEHYDROGENASE 1; 11BETA HYDROXYSTEROID DEHYDROGENASE 2; 7 HYDROXYSTEROID; 7 HYDROXYSTEROL; 7 KETOSTEROID; 7 KETOSTEROL; 7 OXOCHOLESTEROL; 7ALPHA HYDROXYPRASTERONE; 7ALPHA HYDROXYPREGNENOLONE; 7BETA HYDROXYCHOLESTEROL; 7BETA HYDROXYPRASTERONE; 7BETA HYDROXYPREGNENOLONE; CHOLESTEROL MONOOXYGENASE (SIDE CHAIN CLEAVING); CORTISONE; CYTOCHROME P450 17; DEHYDROCORTICOSTERONE; HYDROCORTISONE; HYDROXYSTEROID; HYDROXYSTEROID DEHYDROGENASE; MENADIONE; METYRAPONE; NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; OXOSTEROID; PRASTERONE; PREGNENOLONE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; CATALYSIS; DIABETES MELLITUS; ENZYME ACTIVITY; ENZYME METABOLISM; ENZYME SPECIFICITY; ENZYME STRUCTURE; HUMAN; NONHUMAN; OBESITY; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REVIEW; TRANSCRIPTION REGULATION;

11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; AMINO ACID SEQUENCE; ANIMALS; CARBOHYDRATE DEHYDROGENASES; GLUCOCORTICOIDS; HUMANS; MODELS, BIOLOGICAL; NADP; PROTEIN CONFORMATION; SUBSTRATE SPECIFICITY; TOXICOLOGY;

RODENTIA;

EID: 76749116526     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2010.01.007     Document Type: Review

References (173)

1. Sapolsky R.M., Romero L.M., and Munck A.U. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr. Rev. 21 (2000) 55-89
2. Cole T.J., Blendy J.A., Monaghan A.P., Krieglstein K., Schmid W., Aguzzi A., Fantuzzi G., Hummler E., Unsicker K., and Schutz G. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 9 (1995) 1608-1621
3. Odermatt A., Gumy C., Atanasov A.G., and Dzyakanchuk A.A. Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance. J. Steroid Biochem. Mol. Biol. 102 (2006) 222-231
4. John S., Johnson T.A., Sung M.H., Biddie S.C., Trump S., Koch-Paiz C.A., Davis S.R., Walker R., Meltzer P.S., and Hager G.L. Kinetic complexity of the global response to glucocorticoid receptor action. Endocrinology 150 (2009) 1766-1774
5. Fuller P.J., and Funder J.W. Mineralocorticoid and glucocorticoid receptors in human kidney. Kidney Int. 10 (1976) 154-157
6. Arriza J.L., Weinberger C., Cerelli G., Glaser T.M., Handelin B.L., Housman D.E., and Evans R.M. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237 (1987) 268-275
7. Funder J.W., Pearce P.T., Smith R., and Smith A.I. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242 (1988) 583-585
8. Zennaro M.C., Keightley M.C., Kotelevtsev Y., Conway G.S., Soubrier F., and Fuller P.J. Human mineralocorticoid receptor genomic structure and identification of expressed isoforms. J. Biol. Chem. 270 (1995) 21016-21020
9. Yudt M.R., and Cidlowski J.A. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Mol. Endocrinol. 16 (2002) 1719-1726
10. Lu N.Z., and Cidlowski J.A. Glucocorticoid receptor isoforms generate transcription specificity. Trends Cell Biol. 16 (2006) 301-307
11. Charmandari E., Kino T., and Chrousos G.P. Glucocorticoids and their actions: an introduction. Ann. N.Y. Acad. Sci. 1024 (2004) 1-8
12. Walker B.R., Campbell J.C., Fraser R., Stewart P.M., and Edwards C.R. Mineralocorticoid excess and inhibition of 11β-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome. Clin. Endocrinol. (Oxf.) 37 (1992) 483-492
13. Brien T.G. Human corticosteroid binding globulin. Clin. Endocrinol. (Oxf.) 14 (1981) 193-212
14. Persson B., Kallberg Y., Bray J.E., Bruford E., Dellaporta S.L., Favia A.D., Duarte R.G., Jornvall H., Kavanagh K.L., Kedishvili N., Kisiela M., Maser E., Mindnich R., Orchard S., Penning T.M., Thornton J.M., Adamski J., and Oppermann U. The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative. Chem. Biol. Interact. 178 (2009) 94-98
15. Agarwal A.K., Mune T., Monder C., and White P.C. NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney. J. Biol. Chem. 269 (1994) 25959-25962
16. Albiston A.L., Obeyesekere V.R., Smith R.E., and Krozowski Z.S. Cloning and tissue distribution of the human 11β-hydroxysteroid dehydrogenase type 2 enzyme. Mol. Cell Endocrinol. 105 (1994) R11-17
17. Agarwal A.K., Monder C., Eckstein B., and White P.C. Cloning and expression of rat cDNA encoding corticosteroid 11β-dehydrogenase. J. Biol. Chem. 264 (1989) 18939-18943
18. Atanasov A.G., and Odermatt A. Readjusting the glucocorticoid balance: an opportunity for modulators of 11β-hydroxysteroid dehydrogenase type 1 activity?. Endocr. Metabol. Immune Disord. 7 (2007) 125-140
19. Odermatt A., and Atanasov A.G. Mineralocorticoid receptors: emerging complexity and functional diversity. Steroids 74 (2009) 163-171
20. Tomlinson J.W., and Stewart P.M. Modulation of glucocorticoid action and the treatment of type-2 diabetes. Best Pract. Res. 21 (2007) 607-619
21. Boyle C.D., and Kowalski T.J. 11β-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents. Expert Opin. Ther. Pat. 19 (2009) 801-825
22. Fotsch C., and Wang M. Blockade of glucocorticoid excess at the tissue level: inhibitors of 11β-hydroxysteroid dehydrogenase type 1 as a therapy for type 2 diabetes. J. Med. Chem. 51 (2008) 4851-4857
23. St Jean Jr. D.J., Wang M., and Fotsch C. Inhibitors of 11β-HSD1: a potential treatment for the metabolic syndrome. Curr. Top. Med. Chem. 8 (2008) 1508-1523
24. Schnackenberg C.G. 11β-hydroxysteroid dehydrogenase type 1 inhibitors for metabolic syndrome. Curr. Opin. Invest. Drugs (London England) 9 (2008) 295-300
25. Saiah E. The role of 11β-hydroxysteroid dehydrogenase in metabolic disease and therapeutic potential of 11beta-hsd1 inhibitors. Curr. Med. Chem. 15 (2008) 642-649
26. Bray J.E., Marsden B.D., and Oppermann U. The human short-chain dehydrogenase/reductase (SDR) superfamily: a bioinformatics summary. Chem. Biol. Interact. 178 (2009) 99-109
27. Kavanagh K.L., Jornvall H., Persson B., and Oppermann U. Medium- and short-chain dehydrogenase/reductase gene and protein families: the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell Mol. Life Sci. 65 (2008) 3895-3906
28. Filling C., Berndt K.D., Benach J., Knapp S., Prozorovski T., Nordling E., Ladenstein R., Jornvall H., and Oppermann U. Critical residues for structure and catalysis in short-chain dehydrogenases/reductases. J. Biol. Chem. 277 (2002) 25677-25684
29. Lakshmi V., and Monder C. Purification and characterization of the corticosteroid 11β-dehydrogenase component of the rat liver 11β-hydroxysteroid dehydrogenase complex. Endocrinology 123 (1988) 2390-2398
30. Tannin G.M., Agarwal A.K., Monder C., New M.I., and White P.C. The human gene for 11β-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. J. Biol. Chem. 266 (1991) 16653-16658
31. Agarwal A.K., Tusie-Luna M.T., Monder C., and White P.C. Expression of 11β-hydroxysteroid dehydrogenase using recombinant vaccinia virus. Mol. Endocrinol. 4 (1990) 1827-1832
32. Monder C., Lakshmi V., and Miroff Y. Kinetic studies on rat liver 11β-hydroxysteroid dehydrogenase. Biochim. Biophys. Acta 1115 (1991) 23-29
33. Nobel C.S., Dunas F., and Abrahmsen L.B. Purification of full-length recombinant human and rat type 1 11β-hydroxysteroid dehydrogenases with retained oxidoreductase activities. Protein Exp. Purif. 26 (2002) 349-356
34. Walker E.A., Clark A.M., Hewison M., Ride J.P., and Stewart P.M. Functional expression, characterization, and purification of the catalytic domain of human 11β-hydroxysteroid dehydrogenase type 1. J. Biol. Chem. 276 (2001) 21343-21350
35. Blum A., and Maser E. The critical role of the N-terminus of 11β-hydroxysteroid dehydrogenase type 1, as being encoded by exon 1, for enzyme stabilization and activity. Chem. Biol. Interact. 143-144 (2003) 469-480
36. Shafqat N., Elleby B., Svensson S., Shafqat J., Jornvall H., Abrahmsen L., and Oppermann U. Comparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from glucocorticoid resistant (Guinea pig) versus sensitive (human) species. J. Biol. Chem. 278 (2003) 2030-2035
37. Hosfield D.J., Wu Y., Skene R.J., Hilgers M., Jennings A., Snell G.P., and Aertgeerts K. Conformational flexibility in crystal structures of human 11β-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation. J. Biol. Chem. 280 (2005) 4639-4648
38. Ogg D., Elleby B., Norstrom C., Stefansson K., Abrahmsen L., Oppermann U., and Svensson S. The crystal structure of guinea pig 11β-hydroxysteroid dehydrogenase type 1 provides a model for enzyme-lipid bilayer interactions. J. Biol. Chem. 280 (2005) 3789-3794
39. Zhang J., Osslund T.D., Plant M.H., Clogston C.L., Nybo R.E., Xiong F., Delaney J.M., and Jordan S.R. Crystal structure of murine 11β-hydroxysteroid dehydrogenase 1: an important therapeutic target for diabetes. Biochemistry 44 (2005) 6948-6957
40. Berman H.M., Westbrook J., Feng Z., Gililand G., Bhat T.N., Weissig H., Shindyalov I.N., and Bourne P.E. The protein data bank. Nucl. Acid Res. 28 (2000) 235-242
41. Maser E., Volker B., and Friebertshauser J. 11β-hydroxysteroid dehydrogenase type 1 from human liver: dimerization and enzyme cooperativity support its postulated role as glucocorticoid reductase. Biochemistry 41 (2002) 2459-2465
42. Huang C., Wan B., Gao B., Hexige S., and Yu L. Isolation and characterization of novel human short-chain dehydrogenase/reductase SCDR10B which is highly expressed in the brain and acts as hydroxysteroid dehydrogenase. Acta Biochim. Polonica 56 (2009) 279-289
43. Frick C., Atanasov A.G., Arnold P., Ozols J., and Odermatt A. Appropriate function of 11β-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum lumen is dependent on its N-terminal region sharing similar topological determinants with 50-kDa esterase. J. Biol. Chem. 279 (2004) 31131-31138
44. Odermatt A., Arnold P., Stauffer A., Frey B.M., and Frey F.J. The N-terminal anchor sequences of 11β-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane. J. Biol. Chem. 274 (1999) 28762-28770
45. Filling C., Nordling E., Benach J., Berndt K.D., Ladenstein R., Jornvall H., and Oppermann U. Structural role of conserved Asn179 in the short-chain dehydrogenase/reductase scaffold. Biochem. Biophys. Res. Commun. 289 (2001) 712-717
46. Blum A., Martin H.J., and Maser E. Human 11β-hydroxysteroid dehydrogenase type 1 is enzymatically active in its nonglycosylated form. Biochem. Biophys. Res. Commun. 276 (2000) 428-434
47. Arampatzis S., Kadereit B., Schuster D., Balazs Z., Schweizer R.A., Frey F.J., Langer T., and Odermatt A. Comparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from six species. J. Mol. Endocrinol. 35 (2005) 89-101
48. Agarwal A.K., Mune T., Monder C., and White P.C. Mutations in putative glycosylation sites of rat 11β-hydroxysteroid dehydrogenase affect enzymatic activity. Biochim. Biophys. Acta 1248 (1995) 70-74
49. Tanaka N., Nonaka T., Tanabe T., Yoshimoto T., Tsuru D., and Mitsui Y. Crystal structures of the binary and ternary complexes of 7α-hydroxysteroid dehydrogenase from Escherichia coli. Biochemistry 35 (1996) 7715-7730
50. Mazza C., Breton R., Housset D., and Fontecilla-Camps J.C. Unusual charge stabilization of NADP+ in 17β-hydroxysteroid dehydrogenase. J. Biol. Chem. 273 (1998) 8145-8152
51. Arnold P., Tam S., Yan L., Baker M.E., Frey F.J., and Odermatt A. Glutamate-115 renders specificity of human 11β-hydroxysteroid dehydrogenase type 2 for the cofactor NAD(+). Mol. Cell Endocrinol. 201 (2003) 177-187
52. Sahni-Arya B., Flynn M.J., Bergeron L., Salyan M.E., Pedicord D.L., Golla R., Ma Z., Wang H., Seethala R., Wu S.C., Li J.J., Nayeem A., Gates C., Hamann L.G., Gordon D.A., and Blat Y. Cofactor-specific modulation of 11β-hydroxysteroid dehydrogenase 1 inhibitor potency. Biochim. Biophys. Acta 1774 (2007) 1184-1191
53. Maser E., and Bannenberg G. The purification of 11β-hydroxysteroid dehydrogenase from mouse liver microsomes. J. Steroid Biochem. Mol. Biol. 48 (1994) 257-263
54. Condon J., Ricketts M.L., Whorwood C.B., and Stewart P.M. Ontogeny and sexual dimorphic expression of mouse type 2 11β-hydroxysteroid dehydrogenase. Mol. Cell Endocrinol. 127 (1997) 121-128
55. Veech R.L., Eggleston L.V., and Krebs H.A. The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver. Biochem. J. 115 (1969) 609-619
56. Williamson D.H., Lund P., and Krebs H.A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem. J. 103 (1967) 514-527
57. Pollak N., Niere M., and Ziegler M. NAD Kinase Levels Control the NADPH Concentration in Human Cells. J. Biol. Chem. 282 (2007) 33562-33571
58. Dzyakanchuk A.A., Balazs Z., Nashev L.G., Amrein K.E., and Odermatt A. 11β-Hydroxysteroid dehydrogenase 1 reductase activity is dependent on a high ratio of NADPH/NADP(+) and is stimulated by extracellular glucose. Mol. Cell Endocrinol. 301 (2009) 137-141
59. Agarwal A.K., and Auchus R.J. Minireview: cellular redox state regulates hydroxysteroid dehydrogenase activity and intracellular hormone potency. Endocrinology 146 (2005) 2531-2538
60. Atanasov A.G., Nashev L.G., Schweizer R.A., Frick C., and Odermatt A. Hexose-6-phosphate dehydrogenase determines the reaction direction of 11β-hydroxysteroid dehydrogenase type 1 as an oxoreductase. FEBS Lett. 571 (2004) 129-133
61. Banhegyi G., Benedetti A., Fulceri R., and Senesi S. Cooperativity between 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the lumen of the endoplasmic reticulum. J. Biol. Chem. 279 (2004) 27017-27021
62. Bujalska I.J., Draper N., Michailidou Z., Tomlinson J.W., White P.C., Chapman K.E., Walker E.A., and Stewart P.M. Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11β-hydroxysteroid dehydrogenase type 1. J. Mol. Endocrinol. 34 (2005) 675-684
63. Lavery G.G., Walker E.A., Draper N., Jeyasuria P., Marcos J., Shackleton C.H., Parker K.L., White P.C., and Stewart P.M. Hexose-6-phosphate dehydrogenase knock-out mice lack 11β-hydroxysteroid dehydrogenase type 1-mediated glucocorticoid generation. J. Biol. Chem. 281 (2006) 6546-6551
64. Bujalska I.J., Walker E.A., Hewison M., and Stewart P.M. A switch in dehydrogenase to reductase activity of 11β-hydroxysteroid dehydrogenase type 1 upon differentiation of human omental adipose stromal cells. J. Clin. Endocrinol. Metab. 87 (2002) 1205-1210
65. Draper 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., Malunowicz E., White P.C., Hewison M., Mason P.J., Connell J.M., Shackleton C.H., and Stewart P.M. Mutations in the genes encoding 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat. Genet. 34 (2003) 434-439
66. De Sousa Peixoto R.A., Turban S., Battle J.H., Chapman K.E., Seckl J.R., and Morton N.M. Preadipocyte 11β-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in vivo. Endocrinology 149 (2008) 1861-1868
67. Marcolongo P., Senesi S., Gava B., Fulceri R., Sorrentino V., Margittai E., Lizak B., Csala M., Banhegyi G., and Benedetti A. Metyrapone prevents cortisone-induced preadipocyte differentiation by depleting luminal NADPH of the endoplasmic reticulum. Biochem. Pharmacol. 76 (2008) 382-390
68. Cooper M.S., Bujalska I., Rabbitt E., Walker E.A., Bland R., Sheppard M.C., Hewison M., and Stewart P.M. Modulation of 11β-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation. J. Bone Miner. Res. 16 (2001) 1037-1044
69. Gomez-Sanchez E.P., Romero D.G., de Rodriguez A.F., Warden M.P., Krozowski Z., and Gomez-Sanchez C.E. Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase-1 tissue distribution in the rat. Endocrinology 149 (2008) 525-533
70. Mason P.J., Stevens D., Diez A., Knight S.W., Scopes D.A., and Vulliamy T.J. Human hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) encoded at 1p36: coding sequence and expression. Blood Cells Mol. Dis. 25 (1999) 30-37
71. Ozols J. Isolation and the complete amino acid sequence of lumenal endoplasmic reticulum glucose-6-phosphate dehydrogenase. Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 5302-5306
72. Banhegyi G., Csala M., and Benedetti A. Hexose-6-phosphate dehydrogenase: linking endocrinology and metabolism in the endoplasmic reticulum. J. Mol. Endocrinol. 42 (2009) 283-289
73. Piccirella S., Czegle I., Lizak B., Margittai E., Senesi S., Papp E., Csala M., Fulceri R., Csermely P., Mandl J., Benedetti A., and Banhegyi G. Uncoupled redox systems in the lumen of the endoplasmic reticulum. Pyridine nucleotides stay reduced in an oxidative environment. J. Biol. Chem. 281 (2006) 4671-4677
74. Ferguson S.E., Pallikaros Z., Michael A.E., and Cooke B.A. The effects of different culture media, glucose, pyridine nucleotides and adenosine on the activity of 11β-hydroxysteroid dehydrogenase in rat Leydig cells. Mol. Cell Endocrinol. 158 (1999) 37-44
75. Ge R.S., and Hardy M.P. Initial predominance of the oxidative activity of type I 11β-hydroxysteroid dehydrogenase in primary rat Leydig cells and transfected cell lines. J. Androl. 21 (2000) 303-310
76. Zhang Y.L., Zhong X., Gjoka Z., Li Y., Stochaj W., Stahl M., Kriz R., Tobin J.F., Erbe D., and Suri V. H6PDH interacts directly with 11β-HSD1: implications for determining the directionality of glucocorticoid catalysis. Arch. Biochem. Biophys. 483 (2009) 45-54
77. Lavery G.G., Hauton D., Hewitt K.N., Brice S.M., Sherlock M., Walker E.A., and Stewart P.M. Hypoglycemia with enhanced hepatic glycogen synthesis in recombinant mice lacking hexose-6-phosphate dehydrogenase. Endocrinology 148 (2007) 6100-6106
78. Lavery G.G., Walker E.A., Turan N., Rogoff D., Ryder J.W., Shelton J.M., Richardson J.A., Falciani F., White P.C., Stewart P.M., Parker K.L., and McMillan D.R. Deletion of hexose-6-phosphate dehydrogenase activates the unfolded protein response pathway and induces skeletal myopathy. J. Biol. Chem. 283 (2008) 8453-8461
79. Bujalska I.J., Hewitt K.N., Hauton D., Lavery G.G., Tomlinson J.W., Walker E.A., and Stewart P.M. Lack of hexose-6-phosphate dehydrogenase impairs lipid mobilization from mouse adipose tissue. Endocrinology 149 (2008) 2584-2591
80. Atanasov A.G., Nashev L.G., Gelman L., Legeza B., Sack R., Portmann R., and Odermatt A. Direct protein-protein interaction of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the endoplasmic reticulum lumen. Biochim. Biophys. Acta 1783 (2008) 1536-1543
81. Murphy B.E. Demonstration of novel compounds in human fetal tissues and a consideration of their possible role in parturition. Am. J. Obstet. Gynecol. 139 (1981) 353-358
82. Souness G.W., Latif S.A., Laurenzo J.L., and Morris D.J. 11α- and 11β-hydroxyprogesterone, potent inhibitors of 11β-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat. Endocrinology 136 (1995) 1809-1812
83. Morris D.J., and Souness G.W. Endogenous 11β-hydroxysteroid dehydrogenase inhibitors and their role in glucocorticoid Na+ retention and hypertension. Endocr. Res. 22 (1996) 793-801
84. Brem A.S., Bina R.B., King T., and Morris D.J. 11β-OH-progesterone affects vascular glucocorticoid metabolism and contractile response. Hypertension 30 (1997) 449-454
85. Galigniana M.D., Vicent G.P., Burton G., and Lantos C.P. Features of the shuttle pair 11 beta-hydroxyprogesterone-11-ketoprogesterone. Steroids 62 (1997) 358-364
86. Burton G., Galigniana M., De Lavallaz S., Brachet-Cota A.L., Sproviero E.M., Ghini A.A., Lantos C.P., and Damasco M.C. Sodium-retaining activity of some natural and synthetic 21-deoxysteroids. Mol. Pharmacol. 47 (1995) 535-543
87. Honour J. The possible involvement of intestinal bacteria in steroidal hypertension. Endocrinology 110 (1982) 285-287
88. Bokkenheuser V.D., Winter J., Honour J.W., and Shackleton C.H. Reduction of aldosterone by anaerobic bacteria: origin of urinary 21-deoxy metabolites in man. J. Steroid Biochem. Mol. Biol. 11 (1979) 1145-1149
89. Heap R.B., Holzbauer M., and Newport H.M. Adrenal secretion rates of C-19 and C-21 steroids before and after hypophysectomy in the pig and the dog. J. Endocrinol. 36 (1966) 159-176
90. Burton P.J., and Waddell B.J. Dual function of 11β-hydroxysteroid dehydrogenase in placenta: modulating placental glucocorticoid passage and local steroid action. Biol. Reprod. 60 (1999) 234-240
91. Ganis F.M., Axelrod L.R., and Miller L.L. The metabolism of hydrocortisone by kidney tissue in vitro. J. Biol. Chem. 218 (1956) 841-848
92. Kornel L. Colocalization of 11β-hydroxysteroid dehydrogenase and mineralocorticoid receptors in cultured vascular smooth muscle cells. Am. J. Hypertens. 7 (1994) 100-103
93. Morris D.J., Latif S.A., Hardy M.P., and Brem A.S. Endogenous inhibitors (GALFs) of 11β-hydroxysteroid dehydrogenase isoforms 1 and 2: derivatives of adrenally produced corticosterone and cortisol. J. Steroid Biochem. Mol. Biol. 104 (2007) 161-168
94. Latif S.A., Pardo H.A., Hardy M.P., and Morris D.J. Endogenous selective inhibitors of 11β-hydroxysteroid dehydrogenase isoforms 1 and 2 of adrenal origin. Mol. Cell Endocrinol. 243 (2005) 43-50
95. Wang G.M., Ge R.S., Latif S.A., Morris D.J., and Hardy M.P. Expression of 11β-hydroxylase in rat Leydig cells. Endocrinology 143 (2002) 621-626
96. Leckie C.M., Welberg L.A., and Seckl J.R. 11β-hydroxysteroid dehydrogenase is a predominant reductase in intact rat Leydig cells. J. Endocrinol. 159 (1998) 233-238
97. Gao H.B., Ge R.S., Lakshmi V., Marandici A., and Hardy M.P. Hormonal regulation of oxidative and reductive activities of 11β-hydroxysteroid dehydrogenase in rat Leydig cells. Endocrinology 138 (1997) 156-161
98. Gao H.B., Shan L.X., Monder C., and Hardy M.P. Suppression of endogenous corticosterone levels in vivo increases the steroidogenic capacity of purified rat Leydig cells in vitro. Endocrinology 137 (1996) 1714-1718
99. Claus R., Lacorn M., Welter H., Lekhkota O., Messe N., Wagner A., and Bergmann M. Expression of 11β-hydroxysteroid-dehydrogenase 2 in Sertoli cells of boar testes. Mol. Cell Endocrinol. 272 (2007) 86-92
100. Honda Y., Ohno S., and Nakajin S. Leydig cells from neonatal pig testis abundantly express 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2 and effectively inactivate cortisol to cortisone. J. Steroid Biochem. Mol. Biol. 108 (2008) 91-101
101. Ge R.S., Dong Q., Sottas C.M., Latif S.A., Morris D.J., and Hardy M.P. Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol. Cell Endocrinol. 243 (2005) 35-42
102. Hu G.X., Lin H., Sottas C.M., Morris D.J., Hardy M.P., and Ge R.S. Inhibition of 11β-hydroxysteroid dehydrogenase enzymatic activities by glycyrrhetinic acid in vivo supports direct glucocorticoid-mediated suppression of steroidogenesis in Leydig cells. J. Androl. 29 (2008) 345-351
103. Gao H.B., Tong M.H., Hu Y.Q., Guo Q.S., Ge R., and Hardy M.P. Glucocorticoid induces apoptosis in rat Leydig cells. Endocrinology 143 (2002) 130-138
104. Monder C., Miroff Y., Marandici A., and Hardy M.P. 11β-Hydroxysteroid dehydrogenase alleviates glucocorticoid-mediated inhibition of steroidogenesis in rat Leydig cells. Endocrinology 134 (1994) 1199-1204
105. Rebuffat A.G., Tam S., Nawrocki A.R., Baker M.E., Frey B.M., Frey F.J., and Odermatt A. The 11-ketosteroid 11-ketodexamethasone is a glucocorticoid receptor agonist. Mol. Cell Endocrinol. 214 (2004) 27-37
106. Hampl R., Morfin R., and Starka L. Minireview 7-hydroxylated derivatives of dehydroepiandrosterone: what are they good for?. Endocr. Regul. 31 (1997) 211-218
107. Yau J.L., Rasmuson S., Andrew R., Graham M., Noble J., Olsson T., Fuchs E., Lathe R., and Seckl J.R. Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease. Neuroscience 121 (2003) 307-314
108. Kim S.B., Chalbot S., Pompon D., Jo D.H., and Morfin R. The human cytochrome P4507B1: catalytic activity studies. J. Steroid Biochem. Mol. Biol. 92 (2004) 383-389
109. Stiles A.R., McDonald J.G., Bauman D.R., and Russell D.W. CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. J. Biol. Chem. 284 (2009) 28485-28489
110. Shi J., Schulze S., and Lardy H.A. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids 65 (2000) 124-129
111. Pringle A.K., Schmidt W., Deans J.K., Wulfert E., Reymann K.G., and Sundstrom L.E. 7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischaemia-induced neuronal damage both in vivo and in vitro. Eur. J. Neurosci. 18 (2003) 117-124
112. Kim S.B., Hill M., Kwak Y.T., Hampl R., Jo D.H., and Morfin R. Neurosteroids: cerebrospinal fluid levels for Alzheimer's disease and vascular dementia diagnostics. J. Clin. Endocrinol. Metab. 88 (2003) 5199-5206
113. Weill-Engerer S., David J.P., Sazdovitch V., Liere P., Schumacher M., Delacourte A., Baulieu E.E., and Akwa Y. In vitro metabolism of dehydroepiandrosterone (DHEA) to 7alpha-hydroxy-DHEA and Delta5-androstene-3beta, 17beta-diol in specific regions of the aging brain from Alzheimer's and non-demented patients. Brain Res. 969 (2003) 117-125
114. Morfin R., and Courchay G. Pregnenolone and dehydroepiandrosterone as precursors of native 7-hydroxylated metabolites which increase the immune response in mice. J. Steroid Biochem. Mol. Biol. 50 (1994) 91-100
115. Dulos J., and Boots A.H. DHEA metabolism in arthritis: a role for the p450 enzyme Cyp7b at the immune-endocrine crossroad. Ann. N.Y. Acad. Sci. 1069 (2006) 401-413
116. Lardy H., Partridge B., Kneer N., and Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 6617-6619
117. Ihler G., and Chami-Stemmann H. 7-oxo-DHEA and Raynaud's phenomenon. Med. Hypotheses 60 (2003) 391-397
118. Sulcova J., Hill M., Masek Z., Ceska R., Novacek A., Hampl R., and Starka L. Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men. Physiol. Res. 50 (2001) 9-18
119. Chalbot S., and Morfin R. Human liver S9 fractions: metabolism of dehydroepiandrosterone, epiandrosterone, and related 7-hydroxylated derivatives. Drug Metab. Dispos. 33 (2005) 563-569
120. Miller K.K., Cai J., Ripp S.L., Pierce Jr. W.M., Rushmore T.H., and Prough R.A. Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450. Drug Metab. Dispos. 32 (2004) 305-313
121. Lathe R. Steroid and sterol 7-hydroxylation: ancient pathways. Steroids 67 (2002) 967-977
122. Robinzon B., Michael K.K., Ripp S.L., Winters S.J., and Prough R.A. Glucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of dehydroepiandrosterone: a role for 11β-hydroxysteroid dehydrogenases?. Arch. Biochem. Biophys. 412 (2003) 251-258
123. Robinzon B., and Prough R.A. Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: nuclear and microsomal 11β-hydroxysteroid dehydrogenases. Arch. Biochem. Biophys. 442 (2005) 33-40
124. Hult M., Elleby B., Shafqat N., Svensson S., Rane A., Jornvall H., Abrahmsen L., and Oppermann U. Human and rodent type 1 11β-hydroxysteroid dehydrogenases are 7β-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. Cell Mol. Life Sci. 61 (2004) 992-999
125. Schweizer R.A., Zurcher M., Balazs Z., Dick B., and Odermatt A. Rapid hepatic metabolism of 7-ketocholesterol by 11β-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme. J. Biol. Chem. 279 (2004) 18415-18424
126. Nashev L.G., Chandsawangbhuwana C., Balazs Z., Atanasov A.G., Dick B., Frey F.J., Baker M.E., and Odermatt A. Hexose-6-phosphate Dehydrogenase Modulates 11β-Hydroxysteroid Dehydrogenase Type 1-Dependent Metabolism of 7-keto- and 7β-hydroxy-neurosteroids. PLoS One 2 (2007) e561
127. Muller C., Pompon D., Urban P., and Morfin R. Inter-conversion of 7alpha- and 7beta-hydroxy-dehydroepiandrosterone by the human 11β-hydroxysteroid dehydrogenase type 1. J. Steroid Biochem. Mol. Biol. 99 (2006) 215-222
128. Hennebert O., Le Mee S., Pernelle C., and Morfin R. 5Alpha-androstane-3beta, 7alpha,17beta-triol and 5alpha-androstane-3beta,7beta,17beta-triol as substrates for the human 11beta-hydroxysteroid dehydrogenase type 1. Steroids 72 (2007) 855-864
129. Hennebert O., Pernelle C., Ferroud C., and Morfin R. 7alpha- and 7beta-hydroxy-epiandrosterone as substrates and inhibitors for the human 11β-hydroxysteroid dehydrogenase type 1. J. Steroid Biochem. Mol. Biol. 105 (2007) 159-165
130. Balazs Z., Nashev L.G., Chandsawangbhuwana C., Baker M.E., and Odermatt A. Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11β-hydroxysteroid dehydrogenase 1. Mol. Cell Endocrinol. 301 (2009) 117-122
131. Song W., Chen J., Dean W.L., Redinger R.N., and Prough R.A. Purification and characterization of hamster liver microsomal 7alpha-hydroxycholesterol dehydrogenase. Similarity to type I 11β-hydroxysteroid dehydrogenase. J. Biol. Chem. 273 (1998) 16223-16228
132. Schroepfer Jr. G.J. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol. Rev. 80 (2000) 361-554
133. Bjorkhem I., Andersson O., Diczfalusy U., Sevastik B., Xiu R.J., Duan C., and Lund E. Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages. Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 8592-8596
134. Brown A.J., Leong S.L., Dean R.T., and Jessup W. 7-Hydroperoxycholesterol and its products in oxidized low density lipoprotein and human atherosclerotic plaque. J. Lipid Res. 38 (1997) 1730-1745
135. Crisby M., Nilsson J., Kostulas V., Bjorkhem I., and Diczfalusy U. Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques. Biochim. Biophys. Acta 1344 (1997) 278-285
136. Hulten L.M., Lindmark H., Diczfalusy U., Bjorkhem I., Ottosson M., Liu Y., Bondjers G., and Wiklund O. Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages. J. Clin. Invest. 97 (1996) 461-468
137. Hitsumoto T., Takahashi M., Iizuka T., and Shirai K. Clinical significance of serum 7-ketocholesterol concentrations in the progression of coronary atherosclerosis. J. Atheroscler. Thromb. Vasc. 16 (2009) 363-370
138. Brown A.J., and Jessup W. Oxysterols and atherosclerosis. Atherosclerosis 142 (1999) 1-28
139. Hermanowski-Vosatka A., Balkovec J.M., Cheng K., Chen H.Y., Hernandez M., Koo G.C., Le Grand C.B., Li Z., Metzger J.M., Mundt S.S., Noonan H., Nunes C.N., Olson S.H., Pikounis B., Ren N., Robertson N., Schaeffer J.M., Shah K., Springer M.S., Strack A.M., Strowski M., Wu K., Wu T., Xiao J., Zhang B.B., Wright S.D., and Thieringer R. 11β-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice. J. Exp. Med. 202 (2005) 517-527
140. Nuotio-Antar A.M., Hachey D.L., and Hasty A.H. Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice. Am. J. Physiol. 293 (2007) E1517-1528
141. Morton N.M., Holmes M.C., Fievet C., Staels B., Tailleux A., Mullins J.J., and Seckl J.R. Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11β-hydroxysteroid dehydrogenase type 1 null mice. J. Biol. Chem. 276 (2001) 41293-41300
142. Wamil M., Andrew R., Chapman K.E., Street J., Morton N.M., and Seckl J.R. 7-oxysterols modulate glucocorticoid activity in adipocytes through competition for 11β-hydroxysteroid dehydrogenase type. Endocrinology 149 (2008) 5909-5918
143. Hadoke P.W., Iqbal J., and Walker B.R. Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease. Br. J. Pharmacol. 156 (2009) 689-712
144. Felsted R.L., and Bachur N.R. Mammalian carbonyl reductases. Drug Metab. Rev. 11 (1980) 1-60
145. Oppermann U. Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone-reducing enzymes and their role in physiology. Ann. Rev. Pharmacol. Toxicol. 47 (2007) 293-322
146. Hoffmann F., and Maser E. Carbonyl reductases and pluripotent hydroxysteroid dehydrogenases of the short-chain dehydrogenase/reductase superfamily. Drug Metab. Rev. 39 (2007) 87-144
147. Maser E., and Netter K.J. Purification and properties of a metyrapone-reducing enzyme from mouse liver microsomes--this ketone is reduced by an aldehyde reductase. Biochem. Pharmacol. 38 (1989) 3049-3054
148. Maser E., Gebel T., and Netter K.J. Carbonyl reduction of metyrapone in human liver. Biochem. Pharmacol. 42 Suppl. (1991) S93-98
149. Oppermann U.C., Netter K.J., and Maser E. Cloning and primary structure of murine 11β-hydroxysteroid dehydrogenase/microsomal carbonyl reductase. Eur. J. Biochem. 227 (1995) 202-208
150. Maser E., and Bannenberg G. 11β-hydroxysteroid dehydrogenase mediates reductive metabolism of xenobiotic carbonyl compounds. Biochem. Pharmacol. 47 (1994) 1805-1812
151. Sampath-Kumar R., Yu M., Khalil M.W., and Yang K. Metyrapone is a competitive inhibitor of 11β-hydroxysteroid dehydrogenase type 1 reductase. J. Steroid Biochem. Mol. Biol. 62 (1997) 195-199
152. Bannenberg G., Martin H.J., Belai I., and Maser E. 11β-Hydroxysteroid dehydrogenase type 1: tissue-specific expression and reductive metabolism of some anti-insect agent azole analogues of metyrapone. Chem. Biol. Interact. 143-144 (2003) 449-457
153. Oppermann U.C., Maser E., Mangoura S.A., and Netter K.J. Heterogeneity of carbonyl reduction in subcellular fractions and different organs in rodents. Biochem. Pharmacol. 42 Suppl. (1991) S189-195
154. Hult M., Nobel C.S., Abrahmsen L., Nicoll-Griffith D.A., Jornvall H., and Oppermann U.C. Novel enzymological profiles of human 11β-hydroxysteroid dehydrogenase type 1. Chem. Biol. Interact. 130-132 (2001) 805-814
155. Wsol V., Szotakova B., Skalova L., and Maser E. Stereochemical aspects of carbonyl reduction of the original anticancer drug oracin by mouse liver microsomes and purified 11β-hydroxysteroid dehydrogenase type 1. Chem. Biol. Interact. 143-144 (2003) 459-468
156. Szotakova B., Skalova L., Wsol V., and Kvasnieckova E. Reduction of the potential anticancer drug oracin in the rat liver in-vitro. J. Pharm. Pharmacol. 52 (2000) 495-500
157. Wsol V., Szotakova B., Martin H.J., and Maser E. Aldo-keto reductases (AKR) from the AKR1C subfamily catalyze the carbonyl reduction of the novel anticancer drug oracin in man. Toxicology 238 (2007) 111-118
158. Martin H.J., Breyer-Pfaff U., Wsol V., Venz S., Block S., and Maser E. Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics. Drug Metab. Dispos. 34 (2006) 464-470
159. Maser E. Significance of reductases in the detoxification of the tobacco-specific carcinogen NNK. Trends Pharmacol. Sci. 25 (2004) 235-237
160. Maser E., Friebertshauser J., and Volker B. Purification, characterization and NNK carbonyl reductase activities of 11β-hydroxysteroid dehydrogenase type 1 from human liver: enzyme cooperativity and significance in the detoxification of a tobacco-derived carcinogen. Chem. Biol. Interact. 143-144 (2003) 435-448
161. Hecht S.S. Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines. Chem. Res. Toxicol. 11 (1998) 559-603
162. Breyer-Pfaff U., Martin H.J., Ernst M., and Maser E. 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. Drug Metab. Dispos. 32 (2004) 915-922
163. Jez J.M., Bennett M.J., Schlegel B.P., Lewis M., and Penning T.M. Comparative anatomy of the aldo-keto reductase superfamily. Biochem. J. 326 Pt 3 (1997) 625-636
164. Soldan M., Nagel G., Losekam M., Ernst M., and Maser E. Interindividual variability in the expression and NNK carbonyl reductase activity of 11β-hydroxysteroid dehydrogenase 1 in human lung. Cancer Lett. 145 (1999) 49-56
165. Ahrendt S.A., Chow J.T., Yang S.C., Wu L., Zhang M.J., Jen J., and Sidransky D. Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer. Cancer Res. 60 (2000) 3155-3159
166. Valentino R., Tommaselli A.P., Savastano S., Stewart P.M., Ghiggi M.R., Galletti F., Mariniello P., Lombardi G., and Edwards C.R. Alcohol inhibits 11β-hydroxysteroid dehydrogenase activity in rat kidney and liver. Horm. Res. 43 (1995) 176-180
167. Kenneke J.F., Mazur C.S., Ritger S.E., and Sack T.J. Mechanistic investigation of the noncytochrome P450-mediated metabolism of triadimefon to triadimenol in hepatic microsomes. Chem. Res. Toxicol. 21 (2008) 1997-2004
168. Ward W.O., Delker D.A., Hester S.D., Thai S.F., Wolf D.C., Allen J.W., and Nesnow S. Transcriptional profiles in liver from mice treated with hepatotumorigenic and nonhepatotumorigenic triazole conazole fungicides: propiconazole, triadimefon, and myclobutanil. Toxicol. Pathol. 34 (2006) 863-878
169. Mazur C.S., Kenneke J.F., Goldsmith M.R., and Brown C. Contrasting influence of NADPH and a NADPH-regenerating system on the metabolism of carbonyl-containing compounds in hepatic microsomes. Drug Metabol. Dispos. 37 (2009) 1801-1805
170. Maser E., Richter E., and Friebertshauser J. The identification of 11β-hydroxysteroid dehydrogenase as carbonyl reductase of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Eur. J. Biochem./FEBS 238 (1996) 484-489
171. Maser E., Wsol V., and Martin H.J. 11β-hydroxysteroid dehydrogenase type 1: purification from human liver and characterization as carbonyl reductase of xenobiotics. Mol. Cell Endocrinol. 248 (2006) 34-37
172. Wsol V., Szotakova B., Skalova L., and Maser E. The novel anticancer drug oracin: different stereospecificity and cooperativity for carbonyl reduction by purified human liver 11β-hydroxysteroid dehydrogenase type 1. Toxicology 197 (2004) 253-261
173. Maser E. 11β-hydroxysteroid dehydrogenase responsible for carbonyl reduction of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mouse lung microsomes. Cancer Res. 58 (1998) 2996-3003