Dehydroepiandrosterone 7α- and 7β-hydroxylation in mouse brain microsomes. Effects of cytochrome p450 inhibitors and structure-specific inhibition by steroid hormones

Journal of Neuroendocrinology

Volumn 9, Issue 12, 1997, Pages 923-928

  Doostzadeh, J ^a   Cotillon, A C ^a   Morfin, R ^a  

^a École Supérieure d Ingénieurs Géomètres Topographes   (France)

Author keywords

7 hydroxylation; 7 hydroxylation; Cytochrome P450; Dehydroepiandrosterone; Neurosteroid

Indexed keywords

ALPHA NAPHTHOFLAVONE; ANDROSTENEDIOL; ANDROSTENEDIONE; CORTICOSTERONE; CYTOCHROME P450; CYTOCHROME P450 INHIBITOR; EPIANDROSTERONE; KETOCONAZOLE; METYRAPONE; PHENAZONE; PRASTERONE; PREGNENOLONE; PROGESTERONE; STEROID HORMONE; TESTOSTERONE; ENZYME INHIBITOR; HORMONE; STEROID;

ANIMAL CELL; ARTICLE; BRAIN MICROSOME; CONTROLLED STUDY; HYDROXYLATION; IMMUNE RESPONSE; LIVER; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; ANIMAL; BAGG ALBINO MOUSE; BRAIN; DRUG ANTAGONISM; DRUG EFFECT; ENZYME SPECIFICITY; KINETICS; METABOLISM; MICROSOME;

ANIMALS; BRAIN; CYTOCHROME P-450 ENZYME SYSTEM; DEHYDROEPIANDROSTERONE; ENZYME INHIBITORS; HORMONES; HYDROXYLATION; KINETICS; MALE; MICE; MICE, INBRED BALB C; MICROSOMES; STEROIDS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 0031283159     PISSN: 09538194     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2826.1997.00661.x     Document Type: Article

References (31)

1. Robel P, Synguelakis M, Halberg F, Baulieu EE. Persistance d'un rythme circadien de la déhydroépiandrostérone dans le cerveau, mais non dans le plasma, de rats castrés et surrénalectomisés. CR Acad Sci Paris 1986; 303: 235-238.
2. Robel P, Jung-Testas I, Hu ZY, Akwa Y, Sananes N, Kabbadj K, Eychenne B, Sancho MJ, Kang KI, Zucman D, Morfin R, Baulieu EE. Neurosteroids: biosynthesis, and metabolism in cultured rodent glia and neurons. In: Costa E, Paul SM, eds. Neurosteroids and brain function, Fida Research Foundation Series, New York: Thieme Medical, 1991: 18: 147-154.
3. Kalimi M, Shafagoj Y, Loria R, Padgett D, Regelson W. Antiglucocorticoid effects of dehydroepiandrosterone (DHEA). Mol Cell Biochem 1994; 131: 99-104.
4. Loria RM, Inge TH, Cook S, Szakal A, Regelson W. Protection against acute lethal viral infections with native steroid dehydroepiandrosterone (DHEA). J Med Virology 1988; 26: 301-314.
5. Morfin R, Courchay G. (1994) Pregnenolone and dehydroepiandrosterone as precursors of native 7-hydroxylated metabolites which increase the immune response in mice. J Steroid Biochem Mol Biol 1994; 50: 91-100.
6. Padgett DA, Loria RM. In vitro potentiation of lymphocyte activation by dehydroepiandrosterone, androstenendiol, and androstenetriol. J Immunol 1994; 153: 1544-1552.
7. Akwa Y, Morfin R, Robel P, Baulieu EE. (1992) Neurosteroid metabolism: 7α-hydroxylation of dehydroepiandrosterone and pregnenolone by rat brain microsomes. Biochem J 1992; 288: 959-964.
8. Doostzadeh J, Morfin R. Studies of the enzyme complex responsible for pregnenolone and dehydroepiandrosterone 7α-hydroxylation in mouse tissues. Steroids 1996; 61: 613-620.
9. Guiraud JM, Samperez S, Jouan P. Studies on the 5α-androstane-3β, 17β-diol-6α-hydroxylase and on the 5α-androstane-3δ, 17δ-diol-7α-hydroxylase in anterior hypophysis of male rats. Steroids 1982; 40: 625-639.
10. Warner M, Tollet P, Strömstedt M, Carlström K, Gustafsson JÅ. Endocrine regulation of cytochrome P-450 in the rat brain and pituitary gland. J Endocrinol 1989; 122: 341-349.
11. Doostzadeh J, Urban P, Pompon D, Morfin R. Pregnenolone-7β-hydroxylating activities of yeast-expressed mouse cytochrome p450-1A1 and mouse-tissue microsomes. Eur J Biochcm 1996; 242: 641-647.
12. Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Bjoerkhem I, Seckl JR, Lathe R. Steroid modification in brain: hydroxylation of pregnenolone and DHEA by the novel cytochrome P450, CYP7B. J Endocrinol 1997; 152 (suppl): P280.
13. Stapleton G, Steel M, Richarson M, Mason JO, Rose KA, Morris RGM, Lathe R. A novel cytochrome P450 expressed primarily in brain. J Biol Chem 1995; 270: 29739-29745.
14. Hu ZY, Bourreau E, Jung-Testas I, Robel P, Baulieu EE. Neurosteroids: Oligodendrocyte mitochondria convert cholesterol to pregnenolone. Proc Natl Acad Sci USA 1987; 84: 8215-8219.
15. Strömstedt M, Waterman MR. Messenger RNAs encoding steroidogenic enzymes are expressed in rodent brain. Mol Brain Res 1995; 34: 75-88.
16. Akwa Y, Sananès N, Gouézou M, Robel P, Baulieu EE, Le Goascogne C. Astrocytes and neurosteroids: metabolism of pregnenolone and dehydro-epiandrosterone. Regulation by cell density. J Cell Biol 1993; 121: 135-143.
17. Khalil MW, Strutt B, Vachon D, Killinger DW. Effect of dexamethasone and cytochrome P450 inhibitors on the formation of 7α-hydroxy-dehydroepiandrosterone by human adipose stromal cells. J Steroid Biochem Mol Biol 1994; 48: 545-552.
18. Sesardic D, Boobis AR, Murray BP, Murray S, Segurra J. Furafylline is a potent and selective inhibitor of cytochrome P450 1A2 in man. Br J Clin Pharmacol 1990; 29: 651-663.
19. Kunze KL, Trager WF. Isoform-selective mechanism-based inhibition of human cytochrome P450 IA2 by furafylline. Chem Res Toxicol 1993; 6: 649-656.
20. Halpert JR, Guengerich FP, Bend JR, Correia MA. Selective inhibitors of cytochromes P450. Toxicol Appl Pharm 1994; 125: 163-175.
21. Newton DJ, Wang RW, Lu AYH. Cytochrome P450 inhibitors: evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 1994; 23: 154-158.
22. Ciaccio PJ, Duignan DB, Halpert JR. Selective inactivation by chloramphenicol of the major phenobarbital-inducible isozyme of dog liver cytochrome P450. Drug Metab Disp 1987; 15: 852-856.
23. Ravindranath V; Boyd MR. Xenobitic metabolism in brain. Drug Metab Rev 1995; 27: 419-448.
24. Doostzadeh J, Flinois JP, Beaune P, Morfin R. Pregnenolone 7β-hydroxylation by human cytochrome P450 1A1. J Steroid Biochem Mol Biol 1997; 60: 147-152.
25. Strömstedt M, Warner M, Banner CD, MacDonald PC, Gustfsson JÅ. Role of brain cytochrome P450 in regulation of the level of anesthetic steroids in the brain. Mol Pharmacol 1993; 44: 1077-1083.
26. Doostzadeh J, Morfin R. Effects of cytochrome P450 inhibitors and of steroid hormones on the formation of 7-hydroxylated metabolites of pregnenolone in mouse brain microsomes: J Endocrinol 1997; in press.
27. Morfin R, Di Stéfano S, Charles JF, Floch HH. Precursors for 6ζ and 7α-hydroxylations of 5α-androstane-3β, 17β-diol by human normal and hyperplastic prostate. Biochimie 1977; 59: 637-644.
28. Isaacs JT, McDermott IR, Coffey DS. Characterization of two new enzymatic activities of the rat ventral prostate: 5α-androstane-3β, 17β-diol 6α-hydroxylase and 5α-androstane-3β, 17β-diol 7α-hydroxylase. Steroids 1979; 79: 675-692.
29. Zhang J, Akwa Y, Baulieu EE, Sjövall J. 7α-Hydroxylalion of 27-hydroxycholesterol in rat brain microsomes. CR Acad Sci III-vie 1995; 318: 345-349.
30. Martin KO, Budai K, Javitt NB. Cholesterol and 27-hydroxycholesterol 7α-hydroxylation: evidence for two different enzymes. J Lipid Res 1993; 34: 581-588.
31. Segel IH. Biochemical calculations, 2nd edn, New York: John Wiley & Sons Inc, 1976: 233-256.