Sex differences in the expression of hepatic drug metabolizing enzymes

Molecular Pharmacology

Volumn 76, Issue 2, 2009, Pages 215-228

  Waxman, David J ^a   Holloway, Minita G ^a  

^a Boston University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTINEOPLASTIC AGENT; ANTIRETROVIRUS AGENT; CHLORDIAZEPOXIDE; CHLORZOXAZONE; CLOZAPINE; CONTRACEPTIVE AGENT; CYCLOSPORIN; CYTOCHROME P450 3A4; CYTOCHROME P450 ISOENZYME; DESIPRAMINE; DEXTROMETHORPHAN; DIAZEPAM; DRUG METABOLIZING ENZYME; ERYTHROMYCIN; ESTROGEN; GLUCURONOSYLTRANSFERASE; GLUTATHIONE TRANSFERASE; GROWTH HORMONE; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; HYDROCORTISONE; IFOSFAMIDE; METOPROLOL; MIRTAZAPINE; NIFEDIPINE; OLANZAPINE; PARACETAMOL; PROPRANOLOL; STAT5B PROTEIN; SULFOTRANSFERASE;

BODY FAT; BODY WEIGHT; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CONJUGATION; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG GLUCURONIDATION; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SENSITIVITY; ENZYME REGULATION; EPIGENETICS; GENE EXPRESSION; GENETIC POLYMORPHISM; HORMONAL REGULATION; HUMAN; LIVER METABOLISM; NEUROTOXICITY; NONHUMAN; PLASMA VOLUME; PRIORITY JOURNAL; PROTEIN EXPRESSION; PSYCHOMOTOR PERFORMANCE; REVIEW; SEX DIFFERENCE; SIDE EFFECT; SYSTEMATIC REVIEW; UNSPECIFIED SIDE EFFECT;

ANIMALS; FEMALE; GENE EXPRESSION REGULATION; HUMANS; LIVER; MALE; MODELS, BIOLOGICAL; SEX CHARACTERISTICS;

EID: 67650841094     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.109.056705     Document Type: Review

References (205)

1. Agrawal AK and Shapiro BH (2000) Differential expression of gender-dependent hepatic isoforms of cytochrome P-450 by pulse signals in the circulating masculine episodic growth hormone profile of the rat. J Pharmacol Exp Ther 292:228-237.
2. Agrawal AK and Shapiro BH (2001) Intrinsic signals in the sexually dimorphic circulating growth hormone profiles of the rat. Mol Cell Endocrinol 173:167-181.
3. Amador-Noguez D, Zimmerman J, Venable S, and Darlington G (2005) Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice. Biochem Biophys Res Commun 332:1086-1100. (Pubitemid 40798197)
4. Améen C, Lindén D, Larsson BM, Mode A, Holmäng A, and Oscarsson J (2004) Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver. Am J Physiol Endocrinol Metab 287:E1039-E1048. (Pubitemid 39491944)
5. Anderson GD (2005a) Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin Pharmacokinet 44:989-1008.
6. Anderson GD (2005b) Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J Womens Health (Larchmt) 14:19-29. (Pubitemid 40309363)
7. Austin KL, Mather LE, Philpot CR, and McDonald PJ (1980) Intersubject and dose-related variability after intravenous administration of erythromycin. Br J Clin Pharmacol 10:273-279.
8. Bennett E, McGuinness L, Gevers EF, Thomas GB, Robinson IC, Davey HW, and Luckman SM (2005) Hypothalamic STAT proteins: regulation of somatostatin neurones by growth hormone via STAT5b. J Neuroendocrinol 17:186-194. (Pubitemid 40553018)
9. Bigos KL, Pollock BG, Coley KC, Miller del D, Marder SR, Aravagiri M, Kirshner MA, Schneider LS, and Bies RR (2008) Sex, race, and smoking impact olanzapine exposure. J Clin Pharmacol 48:157-165.
10. Buckley DB and Klaassen CD (2007) Tissue- and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice. Drug Metab Dispos 35:121-127.
11. Ceseña TI, Cui TX, Piwien-Pilipuk G, Kaplani J, Calinescu AA, Huo JS, Iñiguez-LluhíJA, Kwok R, and Schwartz J (2007) Multiple mechanisms of growth hormone-regulated gene transcription. Mol Genet Metab 90:126-133. (Pubitemid 46108616)
12. Cheung C, Yu AM, Chen CS, Krausz KW, Byrd LG, Feigenbaum L, Edwards RJ, Waxman DJ, and Gonzalez FJ (2006) Growth hormone determines sexual dimorphism of hepatic cytochrome P450 3A4 expression in transgenic mice. J Pharmacol Exp Ther 316:1328-1334. (Pubitemid 43345309)
13. Cheung L, Andersen M, Gustavsson C, Odeberg J, Fernández- Pérez L, Norstedt G, and Tollet-Egnell P (2007) Hormonal and nutritional regulation of alternative CD36 transcripts in rat liver - a role for growth hormone in alternative exon usage. BMC molecular biology 8:60. (Pubitemid 47209125)
14. Cheung P and Lau P (2005) Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 19:563-573. (Pubitemid 40349431)
15. Choi HK and Waxman DJ (1999) Growth hormone, but not prolactin, maintains, low-level activation of STAT5a and STAT5b in female rat liver. Endocrinology 140:5126-5135. (Pubitemid 30687122)
16. Choi HK and Waxman DJ (2000) Plasma growth hormone pulse activation of hepatic JAK-STAT5 signaling: developmental regulation and role in male-specific liver gene expression. Endocrinology 141:3245-3255.
17. Chouinard S, Yueh MF, Tukey RH, Giton F, Fiet J, Pelletier G, Barbier O, and Bélanger A (2008) Inactivation by UDP-glucuronosyltransferase enzymes: the end of androgen signaling. J Steroid Biochem Mol Biol 109:247-253.
18. Clodfelter KH, Holloway MG, Hodor P, Park SH, Ray WJ, and Waxman DJ (2006) Sex-dependent liver gene expression is extensive and largely dependent upon signal transducer and activator of transcription 5b (STAT5b): STAT5b-dependent activation of male genes and repression of female genes revealed by microarray analysis. Mol Endocrinol 20:1333-1351. (Pubitemid 43801235)
19. Clodfelter KH, Miles GD, Wauthier V, Holloway MG, Zhang X, Hodor P, Ray WJ, and Waxman DJ (2007) Role of STAT5a in regulation of sex-specific gene expression in female but not male mouse liver revealed by microarray analysis. Physiol Genomics 31:63-74. (Pubitemid 47443849)
20. Colby HD, Gaskin JH, and Kitay JI (1973) Requirement of the pituitary gland for gonadal hormone effects on hepatic corticosteroid metabolism in rats and hamsters. Endocrinology 92:769-774.
21. Cotreau MM, von Moltke LL, and Greenblatt DJ (2005) The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet 44:33-60.
22. Court MH, Hao Q, Krishnaswamy S, Bekaii-Saab T, Al-Rohaimi A, von Moltke LL, and Greenblatt DJ (2004) UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther 310:656-665. (Pubitemid 38988911)
23. Cui Y, Hosui A, Sun R, Shen K, Gavrilova O, Chen W, Cam MC, Gao B, Robinson GW, and Hennighausen L (2007) Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration. Hepatology 46:504-513. (Pubitemid 47344786)
24. Darnell JE Jr. (1997) STATs and gene regulation. Science 277:1630-1635.
25. Davey HW, Park SH, Grattan DR, McLachlan MJ, and Waxman DJ (1999) STAT5b-deficient mice are growth hormone pulse-resistant. Role of STAT5b in sex-specific liver p450 expression. J Biol Chem 274:35331-35336.
26. Davey HW, Xie T, McLachlan MJ, Wilkins RJ, Waxman DJ, and Grattan DR (2001) STAT5b is required for GH-induced liver IGF-I gene expression. Endocrinology 142:3836-3841. (Pubitemid 32802654)
27. Delcuve GP, Rastegar M, and Davie JR (2009) Epigenetic control. J Cell Physiol 219:243-250.
28. Delesque-Touchard N, Park SH, and Waxman DJ (2000) Synergistic action of hepatocyte nuclear factors 3 and 6 on CYP2C12 gene expression and suppression by growth hormone-activated STAT5b. Proposed model for female specific expression of CYP2C12 in adult rat liver. J Biol Chem 275:34173-34182. (Pubitemid 30819181)
29. Denef C (1974) Effect of hypophysectomy and pituitary implants at puberty on the sexual differentiation of testosterone metabolism in rat liver. Endocrinology 94:1577-1582.
30. Dhir RN, Dworakowski W, Thangavel C, and Shapiro BH (2006) Sexually dimorphic regulation of hepatic isoforms of human cytochrome p450 by growth hormone. J Pharmacol Exp Ther 316:87-94. (Pubitemid 41832584)
31. Diczfalusy U, Miura J, Roh HK, Mirghani RA, Sayi J, Larsson H, Bodin KG, Allqvist A, Jande M, Kim JW, et al. (2008) 4Beta-hydroxycholesterol is a new endogenous CYP3A marker: relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians. Pharmacogenet Genomics 18:201-208. (Pubitemid 351323234)
32. Edén S (1979) Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology 105:555-560. (Pubitemid 9241039)
33. Eichelbaum M, Ingelman-Sundberg M, and Evans WE (2006) Pharmacogenomics and individualized drug therapy. Annu Rev Med 57:119-137.
34. Endo M, Takahashi Y, Sasaki Y, Saito T, and Kamataki T (2005) Novel gender-related regulation of CYP2C12 gene expression in rats. Mol Endocrinol 19:1181-1190. (Pubitemid 40598101)
35. Engblom D, Kornfeld JW, Schwake L, Tronche F, Reimann A, Beug H, Hennighausen L, Moriggl R, and Schütz G (2007) Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression. Genes Dev 21:1157-1162. (Pubitemid 46789873)
36. Fernández L, Flores-Morales A, Lahuna O, Sliva D, Norstedt G, Haldosén LA, Mode A, and Gustafsson JA (1998) Desensitization of the growth hormone-induced Janus kinase 2 (Jak 2)/signal transducer and activator of transcription 5 (Stat5)-signaling pathway requires protein synthesis and phospholipase C. Endocrinology 139:1815-1824.
37. Fletcher CV, Acosta EP, and Strykowski JM (1994) Gender differences in human pharmacokinetics and pharmacodynamics. J Adolesc Health 15:619-629.
38. Fodor M, Kordon C, and Epelbaum J (2006) Anatomy of the hypophysiotropic somatostatinergic and growth hormone-releasing hormone system minireview. Neurochem Res 31:137-143.
39. Franconi F, Brunelleschi S, Steardo L, and Cuomo V (2007) Gender differences in drug responses. Pharmacol Res 55:81-95.
40. Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, and Wells JA (1992) Rational design of potent antagonists to the human growth hormone receptor. Science 256:1677-1680.
41. Gabriel SM, Roncancio JR, and Ruiz NS (1992) Growth hormone pulsatility and the endocrine milieu during sexual maturation in male and female rats. Neuroendocrinology 56:619-625.
42. Gachon F, Olela FF, Schaad O, Descombes P, and Schibler U (2006) The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4:25-36. (Pubitemid 43942254)
43. Gandhi M, Aweeka F, Greenblatt RM, and Blaschke TF (2004) Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol 44:499-523.
44. Gardmo C and Mode A (2006) In vivo transfection of rat liver discloses binding sites conveying GH-dependent and female-specific gene expression. J Mol Endocrinol 37:433-441. (Pubitemid 46085169)
45. Gebert CA, Park SH, and Waxman DJ (1999) Down-regulation of liver JAK2-STAT5b signaling by the female plasma pattern of continuous growth hormone stimulation. Mol Endocrinol 13:213-227.
46. Gonzalez FJ (2008) Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription. Drug Metab Pharmacokinet 23:2-7.
47. Gray ES, Woodin BR, and Stegeman JJ (1991) Sex differences in hepatic monooxygenases in winter flounder (Pseudopleuronectes americanus) and scup (Stenotomus chrysops) and regulation of P450 forms by estradiol. J Exp Zool 259:330-342.
48. Gray J (2007) Why can't a woman be more like a man? Clin Pharmacol Ther 82:15-17. (Pubitemid 46944207)
49. Grimley PM, Dong F, and Rui H (1999) Stat5a and Stat5b: fraternal twins of signal transduction and transcriptional activation. Cytokine Growth Factor Rev 10:131-157. (Pubitemid 29446377)
50. Gustafsson JA and Stenberg A (1974) Masculinization of rat liver enzyme activities following hypophysectomy. Endocrinology 95:891-896.
51. Handschin C and Meyer UA (2003) Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev 55:649-673. (Pubitemid 37504978)
52. Hanniman EA, Lambert G, Inoue Y, Gonzalez FJ, and Sinal CJ (2006) Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. J Lipid Res 47:2503-2514. (Pubitemid 44936112)
53. Hartman ML, Veldhuis JD, and Thorner MO (1993) Normal control of growth hormone secretion. Horm Res 40:37-47. (Pubitemid 23349942)
54. Hashita T, Sakuma T, Akada M, Nakajima A, Yamahara H, Ito S, Takesako H, and Nemoto N (2008) Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene. Drug Metab Dispos 36:1080-1087. (Pubitemid 351717465)
55. Hay Kraus BL, Greenblatt DJ, Venkatakrishnan K, and Court MH (2000) Evidence for propofol hydroxylation by cytochrome P4502B11 in canine liver microsomes: breed and gender differences. Xenobiotica 30:575-588. (Pubitemid 30449568)
56. Hayhurst GP, Lee YH, Lambert G, Ward JM, and Gonzalez FJ (2001) Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21:1393-1403. (Pubitemid 32114986)
57. Hemenway C and Robins DM (1987) DNase I-hypersensitive sites associated with expression and hormonal regulation of mouse C4 and Slp genes. Proc Natl Acad Sci U S A 84:4816-4820. (Pubitemid 17095840)
58. Henderson CJ and Wolf CR (1991) Evidence that the androgen receptor mediates sexual differentiation of mouse renal cytochrome P450 expression. Biochem J 278:499-503.
59. Herrington J and Carter-Su C (2001) Signaling pathways activated by the growth hormone receptor. Trends Endocrinol Metab 12:252-257. (Pubitemid 33714215)
60. Higashi E, Fukami T, Itoh M, Kyo S, Inoue M, Yokoi T, and Nakajima M (2007) Human CYP2A6 is induced by estrogen via estrogen receptor. Drug Metab Dispos 35:1935-1941. (Pubitemid 47481589)
61. Hines RN, Koukouritaki SB, Poch MT, and Stephens MC (2008) Regulatory polymorphisms and their contribution to interindividual differences in the expression of enzymes influencing drug and toxicant disposition. Drug Metab Rev 40:263-301.
62. Holloway MG, Cui Y, Laz EV, Hosui A, Hennighausen L, and Waxman DJ (2007) Loss of sexually dimorphic liver gene expression upon hepatocyte-specific deletion of Stat5a-Stat5b locus. Endocrinology 148:1977-1986. (Pubitemid 46997034)
63. Holloway MG, Laz EV, and Waxman DJ (2006) Codependence of growth hormoneresponsive, sexually dimorphic hepatic gene expression on signal transducer and activator of transcription 5b and hepatic nuclear factor 4alpha. Mol Endocrinol 20:647-660.
64. Holloway MG, Miles GD, Dombkowski AA, and Waxman DJ (2008) Liver-specific hepatocyte nuclear factor-4alpha deficiency: greater impact on gene expression in male than in female mouse liver. Mol Endocrinol 22:1274-1286.
65. Hosui A and Hennighausen L (2008) Genomic dissection of the cytokine-controlled STAT5 signaling network in liver. Physiol Genomics 34:135-143.
66. Hunt CM, Westerkam WR, and Stave GM (1992) Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 44:275-283.
67. Hwa V, Little B, Adiyaman P, Kofoed EM, Pratt KL, Ocal G, Berberoglu M, and Rosenfeld RG (2005) Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. J Clin Endocrinol Metab 90:4260-4266. (Pubitemid 41058207)
68. Inagaki K, Inagaki M, Kataoka T, Sekido I, Gill MA, and Nishida M (2002) A wide interindividual variability of urinary 6beta-hydroxycortisol to free cortisol in 487 healthy Japanese subjects in near basal condition. Ther Drug Monit 24:722-727. (Pubitemid 35379525)
69. Ingelman-Sundberg M (2004) Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 25:193-200.
70. Ingelman-Sundberg M, Sim SC, Gomez A, and Rodriguez-Antona C (2007) Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 116:496-526. (Pubitemid 350116943)
71. Inoue Y, Yu AM, Yim SH, Ma X, Krausz KW, Inoue J, Xiang CC, Brownstein MJ, Eggertsen G, Björkhem I, et al. (2006) Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4alpha. J Lipid Res 47:215-227. (Pubitemid 43107464)
72. Jaffe CA, Turgeon DK, Lown K, Demott-Friberg R, and Watkins PB (2002) Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans. Am J Physiol Endocrinol Metab 283:E1008-E1015. (Pubitemid 35216960)
73. Jalouli M, Carlsson L, Améen C, Lindén D, Ljungberg A, Michalik L, Edén S, Wahli W, and Oscarsson J (2003) Sex difference in hepatic peroxisome proliferatoractivated receptor alpha expression: influence of pituitary and gonadal hormones. Endocrinology 144:101-109. (Pubitemid 36076098)
74. Jana S and Paliwal J (2007) Molecular mechanisms of cytochrome p450 induction: potential for drug-drug interactions. Curr Protein Pept Sci 8:619-628. (Pubitemid 351266993)
75. Janeczko R, Waxman DJ, Le Blanc GA, Morville A, and Adesnik M (1990) Hormonal regulation of levels of the messenger RNA encoding hepatic P450 2c (IIC11), a constitutive male-specific form of cytochrome P450. Mol Endocrinol 4:295-303. (Pubitemid 20091523)
76. Jansson JO, Edén S, and Isaksson O (1985) Sexual dimorphism in the control of growth hormone secretion. Endocr Rev 6:128-150.
77. Johnson D, al-Shawi R, and Bishop JO (1995) Sexual dimorphism and growth hormone induction of murine pheromone-binding proteins. J Mol Endocrinol 14:21-34.
78. Jover R, Bort R, Gómez-Lechón MJ, and Castell JV (2001) Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting. Hepatology 33:668-675. (Pubitemid 32185230)
79. Jürgens G, Lange KH, Reuther L∅, Rasmussen BB, Brøsen K, and Christensen HR (2002) Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men. Clin Pharmacol Ther 71:162-168. (Pubitemid 34271119)
80. Kahan BD, Kramer WG, Wideman C, Flechner SM, Lorber MI, and Van Buren CT (1986) Demographic factors affecting the pharmacokinetics of cyclosporine estimated by radioimmunoassay. Transplantation 41:459-464. (Pubitemid 16115547)
81. Kato R (1974) Sex-related differences in drug metabolism. Drug Metab Rev 3:1-32.
82. Kato R and Onoda K (1970) Studies on the regulation of the activity of drug oxidation in rat liver microsomes by androgen and estrogen. Biochem Pharmacol 19:1649-1660.
83. Kennedy M (2008) Hormonal regulation of hepatic drug-metabolizing enzyme activity during adolescence. Clin Pharmacol Ther 84:662-673.
84. Kim SK and Novak RF (2007) The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression. Pharmacol Ther 113:88-120.
85. Klaassen CD, Liu L, and Dunn RT 2nd (1998) Regulation of sulfotransferase mRNA expression in male and female rats of various ages. Chem Biol Interact 109:299-313.
86. Klover P and Hennighausen L (2007) Postnatal body growth is dependent on the transcription factors signal transducers and activators of transcription 5a/b in muscle: a role for autocrine/paracrine insulin-like growth factor I. Endocrinology 148:1489-1497. (Pubitemid 46457107)
87. Knight TR, Choudhuri S, and Klaassen CD (2007) Constitutive mRNA expression of various glutathione S-transferase isoforms in different tissues of mice. Toxicol Sci 100:513-524. (Pubitemid 350131378)
88. Kocarek TA, Duanmu Z, Fang HL, and Runge-Morris M (2008) Age- and sexdependent expression of multiple murine hepatic hydroxysteroid sulfotransferase (SULT2A) genes. Biochem Pharmacol 76:1036-1046.
89. Kramer RE, Greiner JW, Rumbaugh RC, Sweeney TD, and Colby HD (1978) Relation of the gonadal hormones to growth hormone actions on hepatic drug metabolism in rats. J Pharmacol Exp Ther 204:247-254.
90. Krecic-Shepard ME, Park K, Barnas C, Slimko J, Kerwin DR, and Schwartz JB (2000) Race and sex influence clearance of nifedipine: results of a population study. Clin Pharmacol Ther 68:130-142. (Pubitemid 30659168)
91. Kwon SH and Workman JL (2008) The heterochromatin protein 1 (HP1) family: put away a bias toward HP1. Mol Cells 26:217-227.
92. Lahuna O, Fernandez L, Karlsson H, Maiter D, Lemaigre FP, Rousseau GG, Gustafsson J, and Mode A (1997) Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone. Proc Natl Acad Sci U S A 94:12309-12313. (Pubitemid 27492524)
93. Lahuna O, Rastegar M, Maiter D, Thissen JP, Lemaigre FP, and Rousseau GG (2000) Involvement of STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) in the transcriptional control of the hnf6 gene by growth hormone. Mol Endocrinol 14:285-294. (Pubitemid 32295397)
94. Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Fackenthal JD, Rogan PK, Ring B, Wrighton SA, et al. (2003) Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 307:906-922. (Pubitemid 37494207)
95. Lax ER, Hoff HG, Ghraf R, Schröder E, and Schriefers H (1974) The role of the hypophysis in the regulation of sex differences in the activities of enzymes involved in hepatic steroid hormone metabolism. Hoppe Seylers Z Physiol Chem 355:1325-1331.
96. Laz EV, Holloway MG, Chen CS, and Waxman DJ (2007) Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver. Endocrinology 148:3327-3337.
97. Laz EV, Sugathan A and Waxman DJ (2009) Dynamic in vivo binding of STAT5 to growth hormone-regulated genes in intact rat liver. Sex-specific binding at low but not high affinity STAT5 sites. Mol Endocrinol doi: 10.1210/me.2008-0449.
98. Lee SJ, Wang-Buhler JL, Cok I, Yu TS, Yang YH, Miranda CL, Lech J, and Buhler DR (1998) Cloning, sequencing, and tissue expression of CYP3A27, a new member of the CYP3A subfamily from embryonic and adult rainbow trout livers. Arch Biochem Biophys 360:53-61. (Pubitemid 29010913)
99. Lemaigre F and Zaret KS (2004) Liver development update: new embryo models, cell lineage control, and morphogenesis. Curr Opin Genet Dev 14:582-590. (Pubitemid 39360307)
100. Levi F and Schibler U (2007) Circadian rhythms: mechanisms and therapeutic implications. Annu Rev Pharmacol Toxicol 47:593-628. (Pubitemid 46272140)
101. Lichanska AM and Waters MJ (2008) How growth hormone controls growth, obesity and sexual dimorphism. Trends Genet 24:41-47.
102. Liddle C, Goodwin BJ, George J, Tapner M, and Farrell GC (1998) Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab 83:2411-2416. (Pubitemid 28503039)
103. Lin JH, Chiba M, Chen IW, Nishime JA, and Vastag KJ (1996) Sex-dependent pharmacokinetics of indinavir: in vivo and in vitro evidence. Drug Metab Dispos 24:1298-1306. (Pubitemid 26427165)
104. Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, and Hennighausen L (1997) Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 11:179-186. (Pubitemid 27081895)
105. Löfgren S, Baldwin RM, Hiratsuka M, Lindqvist A, Carlberg A, Sim SC, Schülke M, Snait M, Edenro A, Fransson-Steen R, et al. (2008) Generation of mice transgenic for human CYP2C18 and CYP2C19: characterization of the sexually dimorphic gene and enzyme expression. Drug Metab Dispos 36:955-962. (Pubitemid 351574895)
106. Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, and Brown M (2008) FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132:958-970.
107. MacGeoch C, Morgan ET, and Gustafsson JA (1985) Hypothalamo-pituitary regulation of cytochrome P-450(15) beta apoprotein levels in rat liver. Endocrinology 117:2085-2092. (Pubitemid 16194265)
108. MacLeod JN, Pampori NA, and Shapiro BH (1991) Sex differences in the ultradian pattern of plasma growth hormone concentrations in mice. J Endocrinol 131:395-399.
109. MacLeod SM, Giles HG, Bengert B, Liu FF, and Sellers EM (1979) Age- and gender-related differences in diazepam pharmacokinetics. J Clin Pharmacol 19: 15-19. (Pubitemid 9126973)
110. Mader RM (2006) Gender specific tumour pharmacology - from kinetics to genetics. Wien Med Wochenschr 156:545-548.
111. Mann HJ (2006) Drug-associated disease: cytochrome P450 interactions. Crit Care Clin 22:329-345, vii.
112. McClellan-Green PD, Linko P, Yeowell HN, and Goldstein JA (1989) Hormonal regulation of male-specific rat hepatic cytochrome P-450g (P-450IIC13) by androgens and the pituitary. J Biol Chem 264:18960-18965. (Pubitemid 19285798)
113. Miners JO, Attwood J, and Birkett DJ (1983) Influence of sex and oral contraceptive steroids on paracetamol metabolism. Br J Clin Pharmacol 16:503-509. (Pubitemid 14239699)
114. Miura A, Yamagata K, Kakei M, Hatakeyama H, Takahashi N, Fukui K, Nammo T, Yoneda K, Inoue Y, Sladek FM, et al. (2006) Hepatocyte nuclear factor-4alpha is essential for glucose-stimulated insulin secretion by pancreatic beta-cells. J Biol Chem 281:5246-5257. (Pubitemid 43847789)
115. Mode A and Gustafsson JA (2006) Sex and the liver - a journey through five decades. Drug Metab Rev 38:197-207. (Pubitemid 43739007)
116. Mode A, Gustafsson JA, Jansson JO, Edén S, and Isaksson O (1982) Association between plasma level of growth hormone and sex differentiation of hepatic steroid metabolism in the rat. Endocrinology 111:1692-1697.
117. Moon YJ, Wang X, and Morris ME (2006) Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 20:187-210. (Pubitemid 43087702)
118. Morgan ET, Goralski KB, Piquette-Miller M, Renton KW, Robertson GR, Chaluvadi MR, Charles KA, Clarke SJ, Kacevska M, Liddle C, et al. (2008) Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab Dispos 36:205-216. (Pubitemid 351185732)
119. Morgan ET, MacGeoch C, and Gustafsson JA (1985) Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16 alpha-hydroxylase cytochrome P-450 apoprotein in the rat. J Biol Chem 260:11895-11898. (Pubitemid 16228343)
120. Murray M (2007) Role of signalling systems in the effects of dietary factors on the expression of mammalian CYPs. Expert Opin Drug Metab Toxicol 3:185-196.
121. Nakayama K, Sudo Y, Sasaki Y, Iwata H, Takahashi M, and Kamataki T (2001) Studies on transcriptional regulation of Cyp3a16 gene in mouse livers by application of direct DNA injection method. Biochem Biophys Res Commun 287:820-824. (Pubitemid 32958542)
122. Nicholas JS and Barron DH (1932) The use of sodium amytal in the production of anesthesia in the rat. J Pharmacol Exp Ther 46:125-129.
123. Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, Rolfe PA, Conboy CM, Gifford DK, and Fraenkel E (2007) Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39:730-732. (Pubitemid 46848594)
124. Ofotokun I (2005) Sex differences in the pharmacologic effects of antiretroviral drugs: potential roles of drug transporters and phase 1 and 2 metabolizing enzymes. Top HIV Med 13:79-83.
125. Ono M, Chia DJ, Merino-Martinez R, Flores-Morales A, Unterman TG, and Rotwein P (2007) Signal transducer and activator of transcription (Stat) 5b-mediated inhibition of insulin-like growth factor binding protein-1 gene transcription: a mechanism for repression of gene expression by growth hormone. Mol Endocrinol 21:1443-1457. (Pubitemid 46984749)
126. Oscarsson J, Olofsson SO, Vikman K, and Edén S (1991) Growth hormone regulation of serum lipoproteins in the rat: different growth hormone regulatory principles for apolipoprotein (apo) B and the sexually dimorphic apo E concentrations. Metabolism 40:1191-1198.
127. Palva ES (1985) Gender-related differences in diazepam effects on performance. Med Biol 63:92-95.
128. Pampori NA, Agrawal AK, and Shapiro BH (1991) Renaturalizing the sexually dimorphic profiles of circulating growth hormone in hypophysectomized rats. Acta Endocrinol (Copenh) 124:283-289.
129. Pampori NA and Shapiro BH (1993) Sexual dimorphism in avian hepatic monooxygenases. Biochem Pharmacol 46:885-890.
130. Pampori NA and Shapiro BH (1996) Feminization of hepatic cytochrome P450s by nominal levels of growth hormone in the feminine plasma profile. Mol Pharmacol 50:1148-1156.
131. Pampori NA and Shapiro BH (1999) Gender differences in the responsiveness of the sex-dependent isoforms of hepatic P450 to the feminine plasma growth hormone profile. Endocrinology 140:1245-1254.
132. Park SH and Waxman DJ (2001) Inhibitory cross-talk between STAT5b and liver nuclear factor HNF3beta. Impact on the regulation of growth hormone pulsestimulated, male-specific liver cytochrome P-450 gene expression. J Biol Chem 276:43031-43039. (Pubitemid 37370985)
133. Park SH, Wiwi CA, and Waxman DJ (2006) Signalling cross-talk between hepatocyte nuclear factor 4alpha and growth-hormone-activated STAT5b. Biochem J 397:159-168.
134. Parkinson A, Mudra DR, Johnson C, Dwyer A, and Carroll KM (2004) The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. Toxicol Appl Pharmacol 199:193-209. (Pubitemid 39208721)
135. Rademaker M (2001) Do women have more adverse drug reactions? Am J Clin Dermatol 2:349-351. (Pubitemid 34017040)
136. Ram PA, Park SH, Choi HK, and Waxman DJ (1996) Growth hormone activation of Stat 1, Stat 3, and Stat 5 in rat liver. Differential kinetics of hormone desensitization and growth hormone stimulation of both tyrosine phosphorylation and serine/threonine phosphorylation. J Biol Chem 271:5929-5940. (Pubitemid 26084458)
137. Ram PA and Waxman DJ (1999) SOCS/CIS protein inhibition of growth hormonestimulated STAT5 signaling by multiple mechanisms. J Biol Chem 274:35553-35561.
138. Ram PA and Waxman DJ (2000) Role of the cytokine-inducible SH2 protein CIS in desensitization of STAT5b signaling by continuous growth hormone. J Biol Chem 275:39487-39496.
139. Ramadoss P, Marcus C, and Perdew GH (2005) Role of the aryl hydrocarbon receptor in drug metabolism. Expert Opin Drug Metab Toxicol 1:9-21.
140. Roberts RK, Desmond PV, Wilkinson GR, and Schenker S (1979) Disposition of chlordiazepoxide: sex differences and effects of oral contraceptives. Clin Pharmacol Ther 25:826-831.
141. Robertson JA, Haldosén LA, Wood TJ, Steed MK, and Gustafsson JA (1990) Growth hormone pretranslationally regulates the sexually dimorphic expression of the prolactin receptor gene in rat liver. Mol Endocrinol 4:1235-1239. (Pubitemid 20352023)
142. Rogers AB, Theve EJ, Feng Y, Fry RC, Taghizadeh K, Clapp KM, Boussahmain C, Cormier KS, and Fox JG (2007) Hepatocellular carcinoma associated with livergender disruption in male mice. Cancer Res 67:11536-11546.
143. Rosenfeld RG, Belgorosky A, Camacho-Hubner C, Savage MO, Wit JM, and Hwa V (2007) Defects in growth hormone receptor signaling. Trends Endocrinol Metab 18:134-141. (Pubitemid 46629026)
144. Rowland JE, Lichanska AM, Kerr LM, White M, d'Aniello EM, Maher SL, Brown R, Teasdale RD, Noakes PG, and Waters MJ (2005) In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol 25:66-77.
145. Rowlinson SW, Yoshizato H, Barclay JL, Brooks AJ, Behncken SN, Kerr LM, Millard K, Palethorpe K, Nielsen K, Clyde-Smith J, et al. (2008) An agonist-induced conformational change in the growth hormone receptor determines the choice of signalling pathway. Nat Cell Biol 10:740-747. (Pubitemid 351780137)
146. Rudling M, Norstedt G, Olivecrona H, Reihnér E, Gustafsson JA, and Angelin B (1992) Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci U S A 89:6983-6987.
147. Rumbaugh RC and Colby HD (1980) Is growth hormone the pituitary feminizing factor mediating the actions of estradiol on hepatic drug and steroid metabolism? Endocrinology 107:719-724.
148. Sakuma T, Endo Y, Mashino M, Kuroiwa M, Ohara A, Jarukamjorn K, and Nemoto N (2002) Regulation of the expression of two female-predominant CYP3A mRNAs (CYP3A41 and CYP3A44) in mouse liver by sex and growth hormones. Arch Biochem Biophys 404:234-242. (Pubitemid 34913554)
149. Sakuma T, Masaki K, Itoh S, Yokoi T, and Kamataki T (1994) Sex-related differences in the expression of cytochrome P450 in hamsters: cDNA cloning and examination of the expression of three distinct CYP2C cDNAs. Mol Pharmacol 45:228-236. (Pubitemid 24063075)
150. Sasaki Y, Takahashi Y, Nakayama K, and Kamataki T (1999) Cooperative regulation of CYP2C12 gene expression by STAT5 and liver-specific factors in female rats. J Biol Chem 274:37117-37124. (Pubitemid 30016786)
151. Scandlyn MJ, Stuart EC, and Rosengren RJ (2008) Sex-specific differences in CYP450 isoforms in humans. Expert Opin Drug Metab Toxicol 4:413-424.
152. Schmidt R, Baumann F, Hanschmann H, Geissler F, and Preiss R (2001) Gender difference in ifosfamide metabolism by human liver microsomes. Eur J Drug Metab Pharmacokinet 26:193-200. (Pubitemid 32988561)
153. Schwartz JB (2007) The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin Pharmacol Ther 82:87-96.
154. Shapiro BH, Agrawal AK, and Pampori NA (1995) Gender differences in drug metabolism regulated by growth hormone. Int J Biochem Cell Biol 27:9-20.
155. Shimizu I, Kohno N, Tamaki K, Shono M, Huang HW, He JH, and Yao DF (2007) Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol 13:4295-4305. (Pubitemid 47377132)
156. Sinues B, Fanlo A, Mayayo E, Carcas C, Vicente J, Arenaz I, and Cebollada A (2008) CYP2A6 activity in a healthy Spanish population: effect of age, sex, smoking, and oral contraceptives. Hum Exp Toxicol 27:367-372.
157. Sinz M, Wallace G, and Sahi J (2008) Current industrial practices in assessing CYP450 enzyme induction: preclinical and clinical. Aaps J 10:391-400.
158. Sjögren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Törnell J, Isaksson OG, Jansson JO, et al. (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci U S A 96:7088-7092. (Pubitemid 29275014)
159. Skett P (1988) Biochemical basis of sex differences in drug metabolism. Pharmacol Ther 38:269-304.
160. Sladek FM (1994) Orphan receptor HNF-4 and liver-specific gene expression. Receptor 4:64.
161. Soldaini E, John S, Moro S, Bollenbacher J, Schindler U, and Leonard WJ (2000) DNA binding site selection of dimeric and tetrameric Stat5 proteins reveals a large repertoire of divergent tetrameric Stat5a binding sites. Mol Cell Biol 20:389-401. (Pubitemid 30002580)
162. Song WC and Melner MH (2000) Steroid transformation enzymes as critical regulators of steroid action in vivo. Endocrinology 141:1587-1589.
163. Srivastava PK and Waxman DJ (1993) Sex-dependent expression and growth hormone regulation of class alpha and class mu glutathione S-transferase mRNAs in adult rat liver. Biochem J 294:159-165.
164. Ström A, Eguchi H, Mode A, Legraverend C, Tollet P, Strömstedt PE, and Gustafsson JA (1994) Characterization of the proximal promoter and two silencer elements in the CYP2C11 gene expressed in rat liver. DNA Cell Biol 13:805-819.
165. Sueyoshi T, Yokomori N, Korach KS, and Negishi M (1999) Developmental action of estrogen receptor-alpha feminizes the growth hormone-Stat5b pathway and expression of Cyp2a4 and Cyp2d9 genes in mouse liver. Mol Pharmacol 56:473-477. (Pubitemid 29406873)
166. Sundseth SS and Waxman DJ (1992) Sex-dependent expression and clofibrate inducibility of cytochrome P450 4A fatty acid omega-hydroxylases. Male specificity of liver and kidney CYP4A2 mRNA and tissue-specific regulation by growth hormone and testosterone. J Biol Chem 267:3915-3921.
167. Szyf M (2007) The dynamic epigenome and its implications in toxicology. Toxicol Sci 100:7-23.
168. Takeuchi T, Tsutsumi O, Nakamura N, Ikezuki Y, Takai Y, Yano T, and Taketani Y (2004) Gender difference in serum bisphenol A levels may be caused by liver UDP-glucuronosyltransferase activity in rats. Biochem Biophys Res Commun 325:549-554. (Pubitemid 39458029)
169. Tanaka E (1999) Gender-related differences in pharmacokinetics and their clinical significance. J Clin Pharm Ther 24:339-346. (Pubitemid 29520783)
170. Tannenbaum GS, Choi HK, Gurd W, and Waxman DJ (2001) Temporal relationship between the sexually dimorphic spontaneous GH secretory profiles and hepatic STAT5 activity. Endocrinology 142:4599-4606. (Pubitemid 33022334)
171. Tannenbaum GS and Martin JB (1976) Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology 98:562-570.
172. Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, and Ihle JN (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93:841-850. (Pubitemid 28257589)
173. Teixeira J and Gil G (1991) Cloning, expression, and regulation of lithocholic acid 6 beta-hydroxylase. J Biol Chem 266:21030-21036. (Pubitemid 21908570)
174. Thangavel C, Dworakowski W, and Shapiro BH (2006) Inducibility of male-specific isoforms of cytochrome p450 by sex-dependent growth hormone profiles in hepatocyte cultures from male but not female rats. Drug Metab Dispos 34:410-419. (Pubitemid 43292550)
175. Thangavel C, Garcia MC, and Shapiro BH (2004) Intrinsic sex differences determine expression of growth hormone-regulated female cytochrome P450s. Mol Cell Endocrinol 220:31-39. (Pubitemid 38765111)
176. Thangavel C and Shapiro BH (2007) A molecular basis for the sexually dimorphic response to growth hormone. Endocrinology 148:2894-2903. (Pubitemid 46984794)
177. Timsit YE and Negishi M (2007) CAR and PXR: the xenobiotic-sensing receptors. Steroids 72:231-246.
178. Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, and Davey HW (1997) Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci U S A 94:7239-7244.
179. Urquhart BL, Tirona RG, and Kim RB (2007) Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol 47:566-578.
180. Veldhuis JD (1998) Neuroendocrine control of pulsatile growth hormone release in the human: relationship with gender. Growth Horm IGF Res 8 (Suppl B):49-59. (Pubitemid 128674870)
181. Veldhuis JD and Bowers CY (2003) Human GH pulsatility: an ensemble property regulated by age and gender. J Endocrinol Invest 26:799-813.
182. Vidal OM, Merino R, Rico-Bautista E, Fernandez-Perez L, Chia DJ, Woelfle J, Ono M, Lenhard B, Norstedt G, Rotwein P, et al. (2007) In vivo transcript profiling and phylogenetic analysis identifies suppressor of cytokine signaling 2 as a direct signal transducer and activator of transcription 5b target in liver. Mol Endocrinol 21:293-311. (Pubitemid 46041708)
183. Vidarsdottir S, Walenkamp MJ, Pereira AM, Karperien M, van Doorn J, van Duyvenvoorde HA, White S, Breuning MH, Roelfsema F, Kruithof MF, et al. (2006) Clinical and biochemical characteristics of a male patient with a novel homozygous STAT5b mutation. J Clin Endocrinol Metab 91:3482-3485. (Pubitemid 44402123)
184. Wallenius K, Sjögren K, Peng XD, Park S, Wallenius V, Liu JL, Umaerus M, Wennbo H, Isaksson O, Frohman L, et al. (2001) Liver-derived IGF-I regulates GH secretion at the pituitary level in mice. Endocrinology 142:4762-4770. (Pubitemid 33022351)
185. Wang J and Huang Y (2007) Pharmacogenomics of sex difference in chemotherapeutic toxicity. Curr Drug Discov Technol 4:59-68. (Pubitemid 47037694)
186. Wang Y and Jiang H (2005) Identification of a distal STAT5-binding DNA region that may mediate growth hormone regulation of insulin-like growth factor-I gene expression. J Biol Chem 280:10955-10963. (Pubitemid 40418397)
187. Watkins PB, Turgeon DK, Jaffe CA, Ho PJ, and Barkan AL (1993) Pulsation frequency of growth hormone may mediate gender differences in CYP3A activity in man (Abstract). Clin Res 41:13219.
188. Wauthier V and Waxman DJ (2008) Sex-specific early growth hormone response genes in rat liver. Mol Endocrinol 22:1962-1974.
189. Waxman DJ (1988) Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression. Biochem Pharmacol 37:71-84.
190. Waxman DJ (1999) P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 369:11-23.
191. Waxman DJ and Azaroff L (1992) Phenobarbital induction of cytochrome P-450 gene expression. Biochem J 281:577-592.
192. Waxman DJ, LeBlanc GA, Morrissey JJ, Staunton J, and Lapenson DP (1988) Adult male-specific and neonatally programmed rat hepatic P-450 forms RLM2 and 2a are not dependent on pulsatile plasma growth hormone for expression. J Biol Chem 263:11396-11406. (Pubitemid 18202962)
193. Waxman DJ and O'Connor C (2006) Growth hormone regulation of sex-dependent liver gene expression. Mol Endocrinol 20:2613-2629. (Pubitemid 44833525)
194. Waxman DJ, Pampori NA, Ram PA, Agrawal AK, and Shapiro BH (1991) Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450. Proc Natl Acad Sci U S A 88:6868-6872.
195. Waxman DJ, Ram PA, Park SH, and Choi HK (1995) Intermittent plasma growth hormone triggers tyrosine phosphorylation and nuclear translocation of a liver-expressed, Stat 5-related DNA binding protein. Proposed role as an intracellular regulator of male-specific liver gene transcription. J Biol Chem 270:13262-13270.
196. Wilson JT (1973) Growth hormone modulation of liver drug metabolic enzyme activity in the rat. I. Effect of the hormone on the content and rate of reduction of microsomal cytochrome P-450. Biochem Pharmacol 22:1717-1728.
197. Wilson JT and Bass A (1973) Growth hormone modulation of liver drug metabolic enzyme activity in the rat. II. Specificity of the hormone effect. Proc Soc Exp Biol Med 143:978-985.
198. Wiwi CA, Gupte M, and Waxman DJ (2004) Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4alpha-deficient mice. Mol Endocrinol 18:1975-1987. (Pubitemid 39006502)
199. Wiwi CA and Waxman DJ (2005) Role of hepatocyte nuclear factors in transcriptional regulation of male-specific CYP2A2. J Biol Chem 280:3259-3268.
200. Wolbold R, Klein K, Burk O, Nüssler 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. (Pubitemid 37221681)
201. Yamazoe Y, Shimada M, Murayama N, Kawano S, and Kato R (1986) The regulation by growth hormone of microsomal testosterone 6 beta-hydroxylase in male rat livers. J Biochem 100:1095-1097. (Pubitemid 17198458)
202. Yang X, Schadt EE, Wang S, Wang H, Arnold AP, Ingram-Drake L, Drake TA, and Lusis AJ (2006) Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 16:995-1004. (Pubitemid 44162259)
203. Yokomori N, Nishio K, Aida K, and Negishi M (1997) Transcriptional regulation by HNF-4 of the steroid 15alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver. J Steroid Biochem Mol Biol 62:307-314. (Pubitemid 27504761)
204. Yokoyama Y, Nimura Y, Nagino M, Bland KI, and Chaudry IH (2005) Current understanding of gender dimorphism in hepatic pathophysiology. J Surg Res 128:147-156. (Pubitemid 41188223)
205. You L (2004) Steroid hormone biotransformation and xenobiotic induction of hepatic steroid metabolizing enzymes. Chem Biol Interact 147:233-246. (Pubitemid 38591494)