Human liver S9 fractions: Metabolism of dehydroepiandrosterone, epiandrosterone, and related 7-hydroxylated derivatives

Drug Metabolism and Disposition

Volumn 33, Issue 4, 2005, Pages 563-569

  Chalbot, Sonia ^a   Morfin, Robert ^a  

^a Bioinformatique et Chimie Moléculaire   (France)

Author keywords

[No Author keywords available]

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE; ANDROSTANEDIONE; EPIANDROSTERONE; PRASTERONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

ARTICLE; CONTROLLED STUDY; DRUG METABOLISM; FEMALE; GAS CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN TISSUE; HYDROXYLATION; LIVER METABOLISM; MALE; MASS SPECTROMETRY; NEUROPROTECTION; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL;

ANDROSTERONE; DEHYDROEPIANDROSTERONE; FEMALE; HUMANS; HYDROXYLATION; LIVER; MALE; SEX FACTORS;

EID: 15344346887     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.104.003004     Document Type: Article

References (38)

1. Blomquist CH (1995) Kinetic analysis of enzymic activities: prediction of multiple forms of 17 beta-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 55:515-524.
2. Brandon EF, Raap CD, Meijerman I, Beijnen JH, and Schellens JH (2003) An update on in vitro test methods in human hepatic drug biotransformation research: pros and cons. Toxicol Appl Pharmacol 189:233-246.
3. Brown RC, Cascio C, and Papadopoulos V (2000a) Neurosteroids: oxidative stress-mediated dehydroepiandrosterone formation in Alzheimer's disease pathology (Abstract). Neurobiol Aging 21:S238.
4. Brown RC, Cascio C, and Papadopoulos V (2000b) Pathways of neurosteroid biosynthesis in cell lines from human brain: regulation of dehydroepiandrosterone formation by oxidative stress and beta-amyloid peptide. J Neurochem 74:847-859.
5. Chalbot S, Trap C, Monin JP, and Morfin R (2002) Use of bioconversion for the preparation of [4-14C]-labeled 7alpha- and 7beta-hydroxylated derivatives of dehydroepiandrosterone and epiandrosterone. Steroids 67:1121-1127.
6. Chambers VEM, Denny WA, Evans JM, Jones ERH, Kasal A, Meakins GD, and Pragnell J (1973) Microbiological hydroxylation of steroids. Part VIII. The pattern of monohydroxylation of diketones and keto-alcohols derived from 5α-androstane with cultures of the fungus, Rhizopus nigricans. J Chem Soc Perkin Trans I 14:1500-1511.
7. Corpechot C, Robel P, Axelson M, Sjovall J, and Baulieu EE (1981) Characterization and measurement of dehydroepiandrosterone sulfate in rat brain. Proc Natl Acad Sci USA 78: 4704-4707.
8. Doostzadeh J, Cotillon AC, Benalycherif A, and Morfin R (1998) Inhibition studies of dehydroepiandrosterone 7 alpha- and 7 beta-hydroxylation in mouse liver microsomes. Steroids 63:608-614.
9. Doostzadeh J, Cotillon AC, and Morfin R (1997) Dehydroepiandrosterone 7 alpha- and 7 beta-hydroxylation in mouse brain microsomes. Effects of cytochrome p450 inhibitors and structure-specific inhibition by steroid hormones. J Neuroendocrinol 9:923-928.
10. Doostzadeh J and Morfin R ( 1996) Studies of the enzyme complex responsible for pregnenolone and dehydroepiandrosterone 7α-hydroxylation in mouse tissues. Steroids 61:613-620.
11. Doostzadeh J and Morfin R (1997) Effects of cytochrome P450 inhibitors and of steroid hormones on the formation of 7-hydroxylated metabolites of pregnenolone in mouse brain microsomes. J Endocrinol 155:343-350.
12. Dudas B, Hanin I, Rose M, and Wulfert E (2004) Protection against inflammatory neurodegeneration and glial cell death by 7beta-hydroxy epiandrosterone, a novel neurosteroid. Neurobiol Dis 15:262-268.
13. Fitzpatrick JL, Ripp SL, Smith NB, Pierce WM Jr, and Prough RA (2001) Metabolism of DHEA by cytochromes P450 in rat and human liver microsomal fractions. Arch Biochem Biophys 389:278-287.
14. Jellinck PH, Lee SJ, and McEwen BS (2001) Metabolism of dehydroepiandrosterone by rat hippocampal cells in culture: possible role of aromatization and 7-hydroxylation in neuroprotection. J Steroid Biochem Mol Biol 78:313-317.
15. Kim SB, Chalbot S, and Morfin R (2004a) Neurosteroids: hallmarks for 7-hydroxylation in the brain. Recent Res Dev Neurosci 1:61-72.
16. Kim SB, Chalbot S, Pompon D, Jo DH, and Morfin R (2004b) The human cytochrome P4507B1: catalytic activity studies. J Steroid Biochem Mol Biol 92:383-389.
17. Kim SB, Hill M, Kwak YT, Hampl R, Jo DH, and Morfin R (2003) Neurosteroids: cerebrospinal fluid levels for Alzheimer's disease and vascular dementia diagnostics. J Clin Endocrinol Metab 88:5199-5206.
18. Lafaye P, Chmielewski V, Nato F, Mazie JC, and Morfin R (1999) The 7alpha-hydroxysteroids produced in human tonsils enhance the immune response to tetanus toxoid and Bordetella pertussis antigens. Biochim Biophys Acta 1472:222-231.
19. Lanthier A and Patwardhan VV (1986) Sex steroids and 5-en-3 beta-hydroxysteroids in specific regions of the human brain and cranial nerves. J Steroid Biochem 25:445-449.
20. Lathe R (2002) Steroid and sterol 7-hydroxylation: ancient pathways. Steroids 67:967-977.
21. Miller KK, Cai J, Ripp SL, Pierce WM Jr, Rushmore TH, and Prough RA (2004) Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450. Drug Metab Dispos 32:305-313.
22. Morfin R and Starka L (2001) Neurosteroid 7-hydroxylation products in the brain. Int Rev Neurobiol 46:79-95.
23. Niwa T, Yabusaki Y, Honma K, Matsuo N, Tatsuta K, Ishibashi F, and Katagiri M (1998) Contribution of human hepatic cytochrome p450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica 28:539-547.
24. Pirog EC and Collins DC (1999) Metabolism of dihydrotestosterone in human liver: importance of 3alpha- and 3beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 84:3217-3221.
25. Pringle A, Angunawela R, Wilde G, Mepham J, Sundstrom L, and Iannotti F (1997) Induction of a 72KDa heat-shock protein following sub-lethal oxygen deprivation in organotypic hippocampal slice cultures. Neuropathol Appl Neurobiol 23:289-298.
26. Pringle A, Schmidt W, Deans J, Wulfert E, Reymann K, and Sundstrom L (2003) 7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischemia-induced neuronal damage both in vivo and in vitro. Eur J Neurosci 18:117-124.
27. Robinzon B, Michael KK, Ripp SL, Winters SJ, and Prough RA (2003) Glucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of dehydroepiandrosterone: a role for 11beta-hydroxysteroid dehydrogenases? Arch Biochem Biophys 412:251-258.
28. Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Bjorkhem I, Seckl J, and Lathe R (1997) Cyp7b, a novel brain cytochrome p450, catalyzes the synthesis of neurosteroids 7 alpha-hydroxy dehydroepiandrosterone and 7 alpha-hydroxy pregnenolone. Proc Natl Acad Sci USA 94:4925-4930.
29. Schwarz M, Lund EG, Lathe R, Bjorkhem I, and Russell DW (1997) Identification and characterization of a mouse oxysterol 7 alpha-hydroxylase cDNA. J Biol Chem 272:23995-24001.
30. Schwarz M, Lund EG, and Russell DW (1998) Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis. Curr Opin Lipidol 9:113-118.
31. Serralta A, Donato MT, Orbis F, Castell JV, Mir J, and Gomez-Lechon MJ (2003) Functionality of cultured human hepatocytes from elective samples, cadaveric grafts and hepatectomies. Toxicol In Vitro 17:769-774.
32. Stapleton G, Steel M, Richardson M, Mason JO, Rose KA, Morris ROM, and Lathe R (1995) A novel cytochrome P450 expressed primarily in brain. J Biol Chem 270:29739-29745.
33. Stevens JC, Hines RN, Gu C, Koukouritaki SB, Manro JR, Tandler PJ, and Zaya MJ (2003) Developmental expression of the major human hepatic CYP3A enzymes. J Pharmacol Exp Ther 307:573-582.
34. 450 in regulation of the level of anesthetic steroids in the brain. Mol Pharmacol 44:1077-1083.
35. Trincal M, Loeper J, Pompon D, Hauw JJ, and Morfin R (2002) DHEA metabolism in the brain: production and effects of the 7alpha-hydroxylated derivative, in DHEA and the Brain (Morfin R ed) pp 117-128, Taylor & Francis, London.
36. Weill-Engerer S, David JP, Sazdovitch V, Liere P, Eychenne B, Pianos A, Schumacher M, Delacourte A, Baulieu EE, and Akwa Y (2002) Neurosteroid quantification in human brain regions: comparison between Alzheimer's and nondemented patients. J Clin Endocrinol Metab 87:5138-5143.
37. Wolbold R, Klein K, Burk O, Nussler AK, Neuhaus P, Eichelbaum M, Schwab M, and Zanger UM (2003) Sex is a major determinant of CYP3A4 expression in human liver. Hepatology 38:978-988.
38. Wu ZL, Martin KO, Javitt NB, and Chiang JYL (1999) Structure and functions of human oxysterol 7 alpha-hydroxylase cDNAs and gene CYP7B1. J Lipid Res 40:2195-2203.