The roles of Aldo-Keto reductases in steroid hormone action

Drug News and Perspectives

Volumn 17, Issue 9, 2004, Pages 563-578

  Bauman, David R ^a   Steckelbroeck, Stephan ^a   Penning, Trevor M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ALDEHYDE KETONE REDUCTASE; ALDOKETOREDCTASE 1C; ALDOKETOREDUCTASE 1C INHIBITOR; ALDOKETOREDUCTASE 1C1; ALDOKETOREDUCTASE 1C2; ALDOKETOREDUCTASE 1C2 INHIBITOR; ALDOKETOREDUCTASE 1C3; ALDOKETOREDUCTASE 1C4; ALDOKETOREDUCTASE 1D1; ALDOKETOREDUCTASE INHIBITOR; ANDROGEN; BENZODIAZEPINE DERIVATIVE; BENZODIAZEPINE RECEPTOR BLOCKING AGENT; CELL NUCLEUS ORPHAN RECEPTOR; CELL NUCLEUS RECEPTOR; ENZYME INHIBITOR; ESTROGEN; FLUMAZENIL; FLUOXETINE; GESTAGEN; GLUCOCORTICOID; HYDROXYSTEROID DEHYDROGENASE; ION CHANNEL; ISOENZYME; NONSTEROID ANTIINFLAMMATORY AGENT; OXIDOREDUCTASE; SEROTONIN UPTAKE INHIBITOR; STEROID HORMONE; STEROID RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANXIETY; BREAST CANCER; DEPRESSION; DRUG DESIGN; DRUG EFFECT; DRUG MECHANISM; DRUG TARGETING; ENDOMETRIOSIS; ENDOMETRIUM CANCER; ENZYME LOCALIZATION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; EPILEPSY; HORMONE ACTION; HUMAN; INSOMNIA; LIGAND BINDING; MEMBRANE CHANNEL; MIGRAINE; NONHUMAN; PREMENSTRUAL SYNDROME; PROSTATE CANCER; PROTEIN EXPRESSION; RECEPTOR BINDING; REGULATORY MECHANISM; REVIEW; STRUCTURE ACTIVITY RELATION;

ALCOHOL OXIDOREDUCTASES; ANIMALS; GONADAL STEROID HORMONES; HUMANS; ISOENZYMES;

EID: 12344300599     PISSN: 02140934     EISSN: None     Source Type: Journal    
DOI: 10.1358/dnp.2004.17.9.872570     Document Type: Review

References (173)

1. Funder, J.W., Pearce, P.T., Smith, R. and Smith, A.I. Mineralocorticoid action: Target tissue specificity is enzyme, not receptor, mediated. Science 1988, 242: 583-5.
2. Andersson, S. and Moghrabi, N. Physiology and molecular genetics of 17beta-hydroxysteroid dehydrogenases. Steroids 1997, 62: 143-7.
3. Usami, N., Yamamoto, T., Shintani, S., Ishikura, S., Higaki, Y., Katagiri, Y. and Hara, A. Substrate specificity of human 3(20)alpha- hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull 2002, 25: 441-5.
4. Biswas, M.G. and Russell, D.W. Expression cloning and characterization of oxidative 17beta and 3alpha-hydroxysteroid dehydrogenase from rat and human prostate. J Biol Chem 1997, 272: 15959-66.
5. Griffin, L.D. and Mellon, S.H. Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci USA 1999, 96: 13512-7.
6. Trauger, J.W., Jiang, A., Stearns, B.A. and LoGrasso, P.V. Kinetics of allopregnanolone formation catalyzed by human 3alpha-hydroxysteroid dehydrogenase type III (AKR1C2). Biochemistry 2002, 41: 13451-9.
7. Matsuura, K., Shiraishi, H., Hara, A., Sato, K., Deyashiki, Y., Ninomiya, M. and Sakai, S. Identification of a principle mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity. J Biochem 1998, 124: 940-6.
8. Baker, M.E. Evolution of 17beta-hydroxysteroid dehydrogenases and their role in androgen, estrogen and retinoid action. Mol Cell Endocrinol 2001, 171: 211-5.
9. Nelson, V.L., Qin, K.N., Rosenfield, R.L. et al. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab 2001, 86: 5925-33.
10. Pelletier, G., Luu-The, V., El-Alfy, M., Li, S. and Labrie, F. Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland. J Mol Endocrinol 2001, 26: 11-9.
11. Deyashiki, Y., Taniguchi, H., Amano, T., Nakayama, T. and Hara, A. Structural and functional comparison of two human liver dihydrodiol dehydrogenases associated with 3 alpha-hydroxysteroid dehydrogenase activity. Biochem J 1992, 282: 741-6.
12. Degtiar, W.G. and Kushlinsky, N.E. 3alpha-Hydroxysteroid dehydrogenase in animal and human tissues. Biochemistry 2001, 66: 318-31.
13. Penning, T.M., Pawlowski, J.E., Schlegel, B.P. et al. Mammalian 3alpha-hydroxysteroid dehydrogenases. Steroids 1996, 61: 508-23.
14. Carson-Jurica, M.A., Schrader, W.T. and O'Malley, B.W. Steroid receptor family: Structure and functions. Endocr Rev 1990, 11: 201-20.
15. Landers, J.P. and Spelsberg, T.C. New concepts in steroid hormone action: Transcription factors, proto-oncogenes, and the cascade model for steroid regulation of gene expression. Crit Rev Eukaryot Gene Expr 1992, 2: 19-63.
16. Laudet, V. Evolution of the nuclear receptor superfamily: Early diversification from an ancestral orphan receptor. J Mol Endocrinol 1997, 19: 207-26.
17. McKenna, N.J. and O'Malley, B.M. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 2002, 108: 465-74.
18. Lin, T.M. and Chang, C. Cloning and characterization of TDD5, an androgen target gene that is differentially repressed by testosterone and dihydrotestosterone. Proc Nat Acad Sci USA 1997, 94: 4988-93.
19. Deslypere, J.P., Young, M., Wilson, J.D. and McPhaul, M.J. Testosterone and 5alpha-dihydrotestoterone interact differently with the androgen receptor to enhance transcription of the MMTV-CAT reporter gene. Mol Cell Endocrinol 1992, 88: 15-22.
20. Labrie, F., Luu-The, V., Labrie, C. and Simard, J. DHEA and its transformation into androgens and estrogens in peripheral target tissues: Intracrinology. Front Neuroendocrinol 2001, 22: 185-212.
21. Penning, T.M. Molecular endocrinology of hydroxysteroid dehydrogenases. Endocr Rev 1997, 3: 281-305.
22. Tomkins, G. Enzymatic mechanisms of hormone metabolism. I. Oxidation and reduction of the steroid nucleus. Recent Prog Horm Res 1956, 12: 125-33.
23. Penning, T.M., Burczynski, M.E., Jez, J.M. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: Functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J 2000, 351: 67-77.
24. Quinkler, M., Johanssen, S., Bumke-Vogt, C., Oelkers, W., Bahr, V. and Diederich, S. Enzyme-mediated protection of the mineralocorticoid receptor against progesterone in the human kidney. Mol Cell Endocrinol 2001, 171: 21-4.
25. Quinkler, M., Bumke-Vogt, C., Meyer, V., Bahr, V., Oelkers, W. and Diedrich, S. The human kidney is a progesterone-metabolizing and androgen-producing organ. J Clin Endocrinol Metab 2003, 88: 2803-9.
26. Stewart, P.M. and Whorwood, C.B. 11beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action. Steroids 1994, 59: 90-5.
27. Albiston, A.L., Obeyesekere, V.R., Smith, R.E. and Krozowski, Z.S. Cloning and tissue distribution of the human 11-HSD type 2 enzyme. Mol Cell Endocrinol 1994, 105: R11-7.
28. Latif, S.A., Hartman, L.R., Souness, G.W. and Morris, D.J. Possible endogenous regulators of steroid inactivating enzymes and glucocorticoid-induced Na+ retention. Steroids 1994, 59: 352-6.
29. Dufort, I., Rheault, P., Huang, X.F., Soucy, P. and Luu-The, V. Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase. Endocrinology 1999, 140: 568-74.
30. Vihko, P., Harkonen, P., Oduwole, O., Torn, S., Kurkela, R., Porvari, K., Pulkka, A. et al. 17beta-Hydroxysteroid dehydrogenases and cancer. J Steroid Biochem Mol Bio 2002, 83: 199-212.
31. Chetyrkin, S.V., Hu, J., Gough, W.H., Dumaual, N. and Kedishvili, N.Y. Further characterization of human microsomal 3alpha-hydroxysteroid dehydrogenase. Arch Biochem Biophys 2001, 386: 1-10.
32. Huang, X.-F. and Luu-The, V. Characterization of the oxidative 3alpha-hydroxysteroid dehydrogenase activity of human recombinant 11-cis retinal dehydrogenase. Biochim Biophys Acta 2001, 1547: 351-8.
33. Huang, X.-F. and Luu-The, V. Modulation of the androgenic response by recombinant human 11-cis retinal dehydrogenase. J Steroid Biochem Mol Biol 2001, 77: 129-33.
34. He, X.Y., Merz, G., Yang.Y.Z., Pullakart, R., Mehta, P., Schulz, H. and Yang, S.Y. Function of human brain short-chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism. Biochim Biophys Acta 2000, 1484: 267-77.
35. Penning, T.M., Bennett, M.J., Smith-Hoog, S., Schlegel, B.P., Jez, J.M. and Lewis, M. Structure and function of 3alpha-hydroxysteroid dehydrogenase. Steroids 1997, 62: 101-11.
36. Askonas, L.J., Ricigliano, J.W. and Penning, T.M. The kinetic mechanism catalysed by homogeneous rat liver 3 alpha-hydroxysteroid dehydrogenase. Evidence for binary and ternary dead-end complexes containing non-steroidal anti-inflammatory drugs. Biochem J 1991, 278(Pt 3): 835-41.
37. Dufort, I., Labrie, F. and Luu-The, V. Human types 1 and 3 3alpha-hydroxysteroid dehydrogenases: Differential lability and tissue distribution. J Clin Endocrinol Metab 2001, 86: 841-6.
38. Matsuura, K., Deyashiki, Y., Sato, K., Ishida, N., Miwa, G. and Hara, A. Identification of amino acid residues responsible for differences in substrate specificity and inhibitor sensitivity between two human liver dihydrodiol dehydrogenase isoenzymes by site-directed mutagenesis. Biochem J 1997, 323: 61-4.
39. Ciaccio, P.J. and Tew, K.D. cDNA and deduced amino acid sequences of a human colon dihydrodiol dehydrogenase. Biochim Biophys Acta 1994, 1186: 129-32.
40. Khanna, M., Qin, K.E., Wang, R.W. and Cheng, K.C. Substrate specificity, gene structure, and tissue-distribution of multiple human 3alpha-hydroxysteroid dehydrogenase. J Biol Chem 1995, 270: 20162-8.
41. Penning, T.M., Mukharji, I., Barrows, S. and Talalay, P. Purification and properties of a 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol and its inhibition by anti-inflammatory drugs. Biochem J 1984, 222: 601-11.
42. Penning, T.M., Smithgall, T.E., Askonas, L.J. and Sharp, R.B. Rat liver 3 alpha-hydroxysteroid dehydrogenase. Steroids 1986, 47: 221-47.
43. Breyer-Pfaff, U. and Nill, K. High-affinity stereoselective reduction of the enantiomers of ketotifen and of ketonic nortriptyline metabolites by aldo-keto reductases from human liver. Biochem Pharm 2000, 59: 249-60.
44. Atalla, A. and Maser, E. Characterization of enzymes participating in carbonyl reduction of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human placenta. Chem Biol Interact 2001, 130-132: 737-48.
45. Stolz, A., Hammond, L., Lou, H., Takikawa, H., Ronk, M. and Shively, J.E. cDNA cloning and expression of the human hepatic bile acid-binding protein. J Biol Chem 1993, 268: 10448-57.
46. Hara, A., Matsuura, K., Tamada, Y., Sato, K., Miyabe, Y., Deyashiki, Y. and Ishida, N. Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells. Biochem J 1996, 313: 373-6.
47. Strauss, J.F., III, Martinez, F. and Kiriakidou, M. Placental steroid hormone synthesis: Unique features and unanswered questions. Biol Reprod 1996, 54: 303-11.
48. Mori, M. and Wiest, W.G. Purification of rat ovary 20alpha-hydroxysteroid dehydrogenase by affinity chromatography. J Steroid Biochem 1979, 11: 1443-9.
49. Ben-Zimra, M., Koler, M., Melamed-Book, N., Arensburg, J., Payne, A.H. and Orly, J. Uterine and placental expression of steroidogenic genes during rodent pregnancy. Mol Cell Endocrinol 2002, 187: 223-31.
50. Miura, R., Shiota, K., Noda, K., Yagi, S., Ogawa, T. and Takahashi, M. Molecular cloning of cDNA for rat ovarian 20alpha-hydroxysteroid dehydrogenase (HSD1). Biochem J 1994, 299: 561-7.
51. Zhang, Y., Dufort, I., Rheault, P. and Luu-The, V. Characterization of a human 20alpha-hydroxysteroid dehydrogenase. J Mol Endocrinol 2000, 25: 221-8.
52. Stolz, A. Endocrinology Meeting 2003, Philadelphia, USA. June 12-15.
53. Lanisnik, T. and Penning, T.M. Serono Foundation-Molecular Steroidogenesis Workshop 2003, Bath, U.K. April 24-27.
54. Couture, J.F., Legrand, P., Cantin, L., Luu-The, V., Labrie, F. and Breton, R. Human 20alpha-hydroxysteroid dehydrogenase: Crystallographic and site-directed mutagenesis studies lead to the identification of an alternative binding site for C21-steroids. J Mol Biol 2003, 331: 593-604.
55. Qin, K.N., New, M.I. and Cheng, K.C. Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 1993, 46: 673-9.
56. Shiraishi, H., Ishikura, S., Matsuura, K., Deyahiki, Y., Ninomiya, M., Kakai, S. and Hara, A. Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA. Biochem J 1998, 334: 399-405.
57. Takikawa, H., Stolz, A., Sugiyama, Y., Yoshida, H. and Kaplowitz, N. Relationship between the newly identified bile acid binder and bile acid oxidoreductases in human liver. J Biol Chem 1990, 265: 2132-6.
58. Dufort, I., Soucy, P., Labrie, F. and Luu-The, V. Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino acids. Biochem Biophys Res Commun 1996, 228: 474-9.
59. Jin, Y., Stayrook, S.E., Albert, R.H., Palackal, N.T., Penning, T.M. and Lewis, M. Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP+ and ursodeoxycholate. Biochemistry 2001, 40: 10161-8.
60. Nahoum, V., Gangloff, A., Legrand, P. et al. Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution. J Biol Chem 2001, 276: 42091-8.
61. Setchell, K.D.R., Suchy, F.J., Weish, M.B., Zimmer-Nechemias, L., Heubi, J. and Balistreri, W.F. Delta-4-3-oxosteroid 5beta-reductase deficiency described in identical twins with neonatal hepatitis. J Clin Invest 1988, 82: 2148-57.
62. Bahar, R.J. and Stolz, A. Bile acid transport. Gastroenterol Clin North Am 1999, 28: 27-57.
63. Steckelbroeck, S., Jin, Y., Gopishetty, S., Oyesanmi, B. and Penning, T.M. Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: Implications for steroid hormone metabolism and activation. J Biol Chem 2004, 279: 10784-95.
64. Rizner, T.L, Lin, H.K., Peehl, D.M., Steckelbroeck, S., Bauman, D.R. and Penning, T.M. Human type 3 3alpha-hydroxysteroid dehydrogenase (Aldo-keto reductase 1C2) and androgen metabolism in prostate cells. Endocrinology 2003, 144: 2922-32.
65. Ji, Q., Chang, L., VanDenBerg, D., Stanczyk, F.Z. and Stolz, A. Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism. Prostate 2003, 54: 275-89.
66. Lin, H.K., Jez, J.M., Schlegel, B.P., Peehl, D.M., Pachter, J.A. and Penning, T.M. Expression and characterization of recombinant type 2 3alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: Demonstration of bifunctional 3alpha/17beta-HSD activity and cellular distribution. Mol Endocrinol 1997, 11: 1971-84.
67. Luu-The, V. Analysis and characteristics of multiple types of human 17beta-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 2001, 76: 143-51.
68. Winters, C.J., Molowa, D.T. and Guzelian, P.S. Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase. Biochemistry 1990, 29: 1080-7.
69. Deyashiki, Y., Ogasawara, A., Nakayama, T., Nakanishi, M., Miyabe, Y., Sato, K. and Hara, A. Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder. Biochem J 1994, 299(Pt 2): 545-52.
70. Deyashiki, Y., Tamada, Y., Miyabe, Y., Nakanishi, M., Matsuura, K. and Hara, A. Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver. J Biochem 1995, 118: 285-90.
71. Ohta, T., Ishikura, S., Shinani, S., Usami, N. and Hara, A. Kinetic alteration of a human dihydrodiol/3alpha-hydroxysteroid dehydrogenase isozyme, AKR1C4, by replacement of histidine-216 with tyrosine or phenylalanine. Biochem J 2000, 352: 685-91.
72. O'Connor, T., Ireland, L.S., Harrison, D.J. and Hayes, J.D. Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principle human aldo-keto reductase AKR1 family members. Biochem J 1999, 343: 487-504.
73. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003, 72: 137-74.
74. Kondo, K.H., Kai, M.H., Setoguchi, Y. et al. Cloning and expression of cDNA of human delta-4-3-oxosteroid 5beta-reductase and substrate specificity of the expressed enzyme. Eur J Biochem 1994, 219: 357-63.
75. Charbonneau, A. and Luu-The, V. Genomic organization of a human 5beta-reductase and its pseudogene and substrate selectivity of the expressed enzyme. Biochim Biophys Acta 2001, 1517: 228-35.
76. Kimura, A., Kondo, K.H., Okuda, K.I. et al. Diagnosis of the first Japanese patient with 3-oxo-delta-4-steroid 5beta-reductase deficiency by use of immunoblot analysis. Eur J Pediatr 1998, 157: 386-90.
77. Milewich, L., Gomez-Sanchez, C., Madden, J.D. and MacDonald, P.C. Isolation and characterization of 5alpha-pregnane-3,20-dione and progesterone in peripheral blood of pregnant women, measurement throughout pregnancy. Gynecol Invest 1975, 6: 291-306.
78. Narayan, P. Benign Prostatic Hyperplasia. Churchill Livingstone, London, 2000.
79. Kaisary, Amir V. Textbook of Prostate Cancer: Pathology, Diagnosis and Treatment. Martin Dunitz, London, 1999.
80. Weiss, Robert E. Management of Prostate Diseases. 2nd ed., Professional Communications, Inc., Oklahoma, 1997.
81. Walsh, P.C. and Wilson, J.D. The induction of prostatic hypertrophy in dog with androstanediol. J Clin Invest 1976, 57: 1093-7.
82. Jacobi, G.H. and Wilson, J.D. The formation of 5alpha-androstane-3alpha, 17alpha-diol by dog prostate. Endocrinology 1976, 99: 602-10.
83. Leihy, M.W., Shaw, G., Wilson, J.D. and Renfree, M.B. Virilization of the urogenital sinus of the tammar wallaby is not unique to 5alpha-androstane- 3alpha, 17alpha-diol. Mol Cell Endocrinol 2001, 181: 111-5.
84. Shaw, G., Renfree, M.B., Leihy, M.W., Shackleton, C.H., Roitman, E. and Wilson, J.D. Prostate formation in a marsupial is mediated by the testicular androgen 5alpha-androstane-3alpha-17alpha-diol. Proc Nat Acad Sci USA 2000, 97: 12256-9.
85. Suzuki, T., Moriya, T., Ishida, T., Kimura, M. and Ohuchi, N. In situ production of estrogens in human breast carcinoma. Breast Cancer 2002, 9: 296-302.
86. Kitawaki, J., Kado, N., Ishihara, H., Koshiba, H., Kitaoka, Y. and Honjo, H. Endometriosis: The pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol 2003, 83: 149-55.
87. Greenwald, P., Barlow, J.J., Nasca, P.C. and Burnett, W.S. Vaginal cancer after maternal treatment with synthetic estrogens. N Engl J Med 1971, 285: 390-2.
88. Herbst, A.L., Ulfelder, H. and Poskanzer, D.C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971, 284: 878-81.
89. Brueggemeier, R.W. Aromatase, aromatase inhibitors, and breast cancer. Am J Ther 2001, 8: 333-44.
90. Bernstein, L. Epidemiology of endocrine-related risk factors for breast cancer. J Mammary Gland Biol Neoplasia 2002, 7: 3-15.
91. Russo, I.H. and Russo, J. Role of hormones in mammary cancer initiation and progression. J Mammary Gland Biol Neoplasia 1998, 3: 49-61.
92. Huggins, C.B. Propositions in hormonal treatment of advanced cancers. JAMA 1965, 192: 1141-5.
93. Penning, T.M., Burczynski, M.E., Jez, J.M. et al. Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3). Mol Cell Endocrinol 2001, 171: 137-49.
94. Luu-The, V., Dufort, I., Pelletier, G. and Labrie, F. Type 5 17beta-hydroxysteroid dehydrogenase: Its role in the formation of androgens in women. Mol Cell Endocrinol 2001, 171: 77-82.
95. Wiebe, J.P. and Lewis, M. Activity and expression of progesterone metabolizing 5alpha-reductase, 20alpha-hydroxysteroid oxidoreductase and 3alpha(beta)-hydroxysteroid oxidoreductase in tumorigenic (MCF-7, MDA-MB-231, T-47D) and non-tumorigenic (MCF-10A) human breast cancer cells. BMC Cancer 2003, 3: 1-15.
96. Vihko, P., Harkonen, P., Oduwole, O. et al. 17 beta-hydroxysteroid dehydrogenases and cancers. J Steroid Biochem Mol Biol 2002, 83: 119-22.
97. Simpson, E.R., Clyne, C., Speed, C., Rubin, G. and Bulun, S. Tissue-specific estrogen biosynthesis and metabolism. Ann NY Acad Sci 2001, 949: 58-67.
98. Ben-Zimra, M., Koler, M., Melamed-Book, N., Arensburg, J., Payne, A.H. and Orly, J. Uterine and placental expression of steroidogenic genes during rodent pregnancy. Mol Cell Endocrinol 2002, 187: 223-31.
99. Chwalisz, K., Brenner, R.M., Fuhrmann, U.U., Hess-Stumpp, H. and Elger, W. Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium. Steroids 2000, 65: 741-51.
100. Devoto, L., Kohen, P., Vega, M. et al. Control of human luteal steroidogenesis. Mol Cell Endocrinol 2002, 186: 137-41.
101. Piccinni, M.P., Beloni, L., Livi, C., Maggi, E., Scarselli, G. and Romagnani, S. Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat Med 1998, 4: 1020-4.
102. Nishizawa, M., Nakajima, T., Yasuda, K., Kanzaki, H., Sasaguri, Y., Watanabe, K. and Ito, S. Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes. Genes Cells 2000, 5: 111-25.
103. Stocco, C.O., Zhong, L., Sugimoto, Y., Ichikawa, A., Lau, L.F. and Gibori, G. Prostaglandin F2alpha-induced expression of 20alpha-hydroxysteroid dehydrogenase involves the transcription factor NUR77. J Biol Chem 2000, 275: 37202-11.
104. Milewich, L., Gant, N.F., Schwarz, B.E., Chen, G.T. and Macdonald, P.C. Initiation of human parturition. IX. Progesterone metabolism by placentas of early and late human gestation. Obstet Gynecol 1978, 51: 278-80.
105. MacDonald, P.C., Schultz, P.M., Duenhoelter, J.H. et al. Initiation of human parturition. I. Mechanism of action of arachidonic acid. Obstet Gynecol 1974, 44: 629-36.
106. Holloway, R.W. Treatment options for endometrial cancer: Experience with topotecan. Gynecol Oncol 2003, 90(3 Pt 2): S28-33.
107. Cormio, G., Capotorto, M., Vagno, G.D., Cazzolla, A., Carriero, C. and Selvaggi, L. Skin metastases in ovarian carcinoma: A report of nine cases and a review of the literature. Gynecol Oncol 2003, 90: 682-5.
108. Gurates, B. and Bulun, S.E. Endometriosis: The ultimate hormonal disease. Semin Reprod Med 2003, 21: 125-34.
109. Zeitoun, K., Takayama, K., Sasano, H. et al. Deficient 17beta-hydroxysteroid dehydrogenase type 2 expression in endometriosis: Failure to metabolize 17beta-estradiol. J Clin Endocrinol Metab 1998, 83: 4474-80.
110. Utsunomiya, H., Suzuki, T., Ito, K. et al. The correlation between the response to progestogen treatment and the expression of progesterone receptor B and 17beta-hydroxysteroid dehydrogenase type 2 in human endometrial carcinoma. Clin Endocrinol 2003, 58: 696-703.
111. Schroder, R. Endometrial hyperplasia in relation to genital function. Am J Obstet Gynecol 1954, 68: 294-309.
112. Desmond, J.C., Mountford, J.C., Drayson, M.T. et al. The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs. Cancer Res 2003, 63: 505-12.
113. Xin, X., Yang, S., Kowalski, J. and Gerritsen, M.E. Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 1999, 274: 9116-21.
114. Bishop-Bailey, D. and Hla, T. Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Delta12,14- prostaglandin J2. J Biol Chem 1999, 274: 17042-8.
115. Staudinger, J.L., Goodwin, B., Jones, S.A. et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 2001, 98: 3369-74.
116. Xie, W., Radominska-Pandya, A., Shi, Y. et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA 2001, 98: 3375-80.
117. Bertilsson, G., Heidrich, J., Svensson, K. et al. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 1998, 95: 12208-13.
118. Selye, H. Correlations between the chemical structure and the pharmacological actions of the steroids. Endocrinology 1942, 30: 437-53.
119. Paul, S.E. and Purdy, R.H. Neuroactive steroids. FASEB J 1992, 6: 2311-22.
120. Majewska, M.D. Neurosteroids: Endogenous bimodal modulators of the GABA-A receptor. Mechanism of action and physiological significance. Prog Neurobiol 1992, 38: 379-95.
121. Joëls, M. Steroid hormones and excitability in the mammalian brain. Front Neuroendocrinol 1997, 18: 2-48.
122. Rupprecht, R. and Holsboer, F. Neuroactive steroids: Mechanism of action and neuropsychopharmacological perspectives. Trends Neurosci 1999, 22: 410-6.
123. Mellon, S.H. and Griffin, L.D. Neurosteroids: Biochemistry and clinical significance. Trends Endocrinol Metab 2002, 13: 35-43.
124. Crawley, J.N., Glowa, J.R., Majewska, M.D. and Paul, S.M. Anxiolytic activity of an endogenous adrenal steroid. Brain Res 1986, 398: 382-5.
125. Bitran, D., Hilvers, R.J. and Kellogg, C.K. Anxiolytic effects of 3alpha-hydroxy-5alpha[beta]-pregnan-20-one: Endogenous metabolites of progesterone that are active at the GABA-A receptor. Brain Res 1991, 561: 157-61.
126. Kokate, T.G., Svensson, B.E. and Rogawski, M.A. Anticonvulsant activity of neurosteroids: Correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 1994, 270: 1223-9.
127. Frye, C.A. and Scalise, T.J. Anti-seizure effects of progesterone and 3alpha,5alpha-THP in kainic and perforant pathway models of epilepsy. Psychoneuroendocrinology 2000, 25: 407-20.
128. Lambert, J.J., Belelli, D., Harney, S.C., Peters, J.A. and Frenguelli, B.G. Modulation of native and recombinant GABA-A receptors by endogenous and synthetic neuroactive steroids. Brain Res Rev 2001, 37: 68-80.
129. Gee, K.W., Bolger, M.B., Brinton, R.E., Coirini, H. and McEwen, B.S. Steroid modulation of the chloride ionophore in rat brain: Structure-activity requirements, regional dependence and mechanism of action. J Pharmacol Exp Ther 1988, 246: 803-12.
130. Harrison, N.L., Majewska, M.D., Harrington, J.W. and Barker, J.L. Structure-activity relationships for steroid interaction with the gamma-aminobutyric acid-A receptor complex. J Pharmacol Exp Ther 1987, 241: 346-53.
131. Peters, J.A., Kirkness, E.F., Callachan, H., Lambert, J.J. and Turner, A.J. Modulation of the GABA-A receptor by depressant barbiturates and pregnane steroids. Br J Pharmacol 1988, 94: 1257-69.
132. Turner, J.P. and Simmonds, M.A. Modulation of the GABA-A receptor complex by steroids in slices of rat cuneate nucleus. Br J Pharmacol 1989, 96: 409-17.
133. Puia, G., Santi, M.R., Vicini, S. et al. Neurosteroids act on recombinant human GABA-A receptors. Neuron 1990, 4: 759-65.
134. Prince, R.J. and Simmonds, M.A. 5beta-pregnan-3beta-ol-20-one, a specific antagonist at the neurosteroid site of the GABA-A receptor-complex. Neurosci Lett 1992, 135: 273-5.
135. Prince, R.J. and Simmonds, M.A. Differential antagonism by epipregnanolone of alphaxalone and pregnanolone potentiation of [3H]flunitrazepam binding suggests more than one class of binding site for steroids at GABA-A receptors. Neuropharmacology 1993, 32: 59-63.
136. Maitra, R. and Reynolds, J.N. Modulation of GABA-A receptor function by neuroactive steroids: Evidence for heterogeneity of steroid sensitivity of recombinant GABA-A receptor isoforms. Can J Physiol Pharmacol 1998, 76: 909-20.
137. Wang, M.D., Bäckstrom, T. and Landgren, S. The inhibitory effects of allopregnanolone and pregnanolone on the population spike, evoked in the rat hippocampal CA1 stratum pyramidale in vitro, can be blocked selectively by epiallopregnanolone. Acta Physiol Scand 2000, 169: 333-41.
138. Wang, M., He, Y., Eisenmann, L.N. et al. 3beta-hydroxypregnane steroids are pregnenolone sulfate-like GABA-A receptor antagonists. J Neurosci 2002, 22: 3366-75.
139. Reedy, D.S. and Rogawski, M.A. Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA-A receptor function and seizure susceptibility. J Neurosci 2002, 22: 3795-805.
140. Penning, T.M. and Talalay, P. Inhibition of a major NAD(P)-linked oxidoreductase from rat liver cytosol by steroidal and nonsteroidal anti-inflammatory agents and by prostaglandins. Proc Natl Acad Sci USA 1983, 80: 4504-8.
141. Rommerts, F.F.G. and van der Molen, H.J. Occurrence and localization of 5alpha-steroid reductase, 3alpha- and 17beta-hydroxysteroid dehydrogenases in hypothalamus and other brain tissues of the male rat. Biochim Biophys Acta 1971, 248: 489-502.
142. Sholiton, L.J., Taylor, B.B. and Lewis, H.P. The uptake and metabolism of labelled testosterone by the brain and pituitary of the male rhesus monkey (Macaca mulatta). Steroids 1974, 24: 537-47.
143. Hanukoglu, I., Karavolas, H.J. and Goy, R.W. Progesterone metabolism in the pineal, brain stem, thalamus and corpus callosum of the female rat. Brain Res 1977, 125: 313-24.
144. Martini, L., Celotti, F. and Melcangi, R.C. Testosterone and progesterone metabolism in the central nervous system: Cellular localization and mechanism of control of the enzymes involved. Cell Mol Neurobiol 1996, 16: 271-82.
145. Mickan, H. Metabolism of 4-14C-progesterone and 4-14C-testosterone in brain of the previable human fetus. Steroids 1972, 19: 659-68.
146. Jenkins, J.S. and Hall, C.J. Metabolism of [14C]testosterone by human foetal and adult brain tissue. J Endocrinol 1977, 74: 425-9.
147. Poletti, A., Negri-Cesi, P., Rabuffetti, M., Colciago, A., Celotti, F. and Martini, L. Transient expression of the 5alpha-reductase type 2 isozyme in the rat brain in late fetal and early postnatal life. Endocrinology 1998, 139: 2171-8.
148. Steckelbroeck, S., Watzka, M., Stoffel-Wagner, B. et al. Expression of the 17beta-hydroxysteroid dehydrogenase type 5 mRNA in the human brain. Mol Cell Endocrinol 2001, 171: 165-8.
149. Stoffel-Wagner, B., Watzka, M., Steckelbroeck, S. et al. Allopregnanolone serum levels and expression of 5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase isoforms in hippocampal and temporal cortex of patients with epilepsy. Epilepsy Res 2003, 54: 11-9.
150. Steckelbroeck, S., Watzka, M., Reichelt, R. et al. Characterization of the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase complex in the human brain. J Clin Endocrinol Metab 2001, 86: 1324-31.
151. Stoffel-Wagner, B., Watzka, M., Steckelbroeck, S. et al. Expression of 5alpha-reductase in the human temporal lobe of children and adults. J Clin Endocrinol Metab 1998, 83: 3636-42.
152. Penning, T.M., Sharp, R.B. and Krieger, N.R. Purification and properties of 3alpha-hydroxysteroid dehydrogenase from rat brain cytosol. Inhibition by nonsteroidal anti-inflammatory drugs and progestins. J Biol Chem 1985, 260: 15266-72.
153. Griffin, L.D. and Mellon, S.H. Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci USA 1999, 96: 13512-7.
154. Higaki, Y., Usami, N., Shintani, S., Ishikura, S., El-Kabbani, O. and Hara, A. Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interactions 2003, 143-144: 503-13.
155. van Broekhoven, F. and Verkes, R.J. Neurosteroids in depression: A review. Psychopharmacology 2003, 165: 97-110.
156. Rapkin, A.J., Morgan, M., Goldman, L., Brann, D.W., Simone, D. and Mahesh, V.B. Progesterone metabolite allopregnanolone in woman with premenstrual syndrome. Obstet Gynecol 1997, 90: 709-14.
157. Monteleone, P., Luisi, S., Tonetti, A. et al. Allopregnanolone concentrations and premenstrual syndrome. Eur J Endocrinol 2000, 142: 269-73.
158. Bicikova, M., Dibbelt, L., Hill, M., Hampl, R. and Starka, L. Allopregnanolone in woman with premenstrual syndrome. Hormone Metab Res 1998, 30: 227-30.
159. Backstrom, T., Andreen, L., Birzniece, V. et al. The role of hormones and hormonal treatments in premenstrual syndrome. CNS Drugs 2003, 17: 325-42.
160. Uzunova, V., Sheline, Y., Davis, J.M., Rasmusson, A., Uzunov, D.P., Costa, E. and Guidotti, A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA 1998, 95: 3239-44.
161. Steiner, M., Steinberg, S., Stewart, D. et al. Fluoxetine in the treatment of premenstrual dysphoria. Canadian fluoxetine/premenstrual dysphoria collaborative study group. N Engl J Med 1995, 332: 1529-34.
162. Su, T.-P., Schmidt, P.J., Danaceau, M.A., Tobin, M.B., Rosenstein, D.L., Murphy D.L. and Rubinow, D.R. Fluoxetine in the treatment of premenstrual dysphoria. Neuropsychopharmacology 1997, 16: 346-56.
163. Uzunov, D.P., Cooper, T.B., Costa, E. and Guidotti, A. Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Proc Natl Acad Sci USA 1996, 93: 12599-604.
164. Khisti, R.T. and Chopde, C.T. Serotonergic agents modulate antidepressant-like effects of the neurosteroid 3alpha-hydroxy-5alpha-pregnan- 20-one in mice. Brain Res 2000, 865: 291-300.
165. Brot, M.D., Akwa, Y., Purdy, R.H., Koob, G.F. and Britton, K.T. The anxiolytic-like effects of the neurosteroid allopregnanolone: Interaction with GABA-A receptors. Eur J Pharmacol 1997, 325: 1-7.
166. Gasior, M., Carter, R.B. and Witkin, J.M. Neuroactive steroids: Potential therapeutic use in neurological and psychiatric disorders. TiPS 1999, 20: 107-12.
167. Hoog, S.S., Pawlowski, J.E., Alzari, P.M., Penning, T.M. and Lewis, M. Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: A member of the aldo-keto reductase superfamily. Proc Natl Acad Sci USA 1994, 91: 2517-21.
168. Bennett, M.J., Schlegel, B.P., Jez, J.M., Penning, T.M. and Lewis, M. Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+. Biochemistry 1996, 35: 10702-11.
169. Bennett, M.J., Albert, R.H., Jez, J.M., Ma, H., Penning, T.M. and Lewis, M. Steroid recognition and regulation of hormone action: Crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Structure 1997, 5: 799-812.
170. Jez, J.M. and Penning, T.M. The aldo-keto reductase (AKR) superfamily: An update. Chem Biol Interact 2001, 130-132: 499-525.
171. Penning, T.M. Molecular determinants of steroid recognition and catalysis in aldo-keto reductases. Lessons from 3alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Bio 1999, 69: 211-25.
172. Schlegel, B.P., Jez, J.M. and Penning, T.M. Mutagenesis of 3
173. Bauman, D.R., Rudnick, S.I., Szewczuk, L.M., Jin, Y., Gopishetty, S. and Penning, T.M. Development of non-steroidal anti-inflammatory drug (NSAID) analogs and steroid carboxylates selective for human aldo-ketoreductase isoforms: Potential antineoplastic agents that work independently of cyclooxygenase isozymes. Mol Pharmacol 2004, Oct 8 (Epub ahead of print).