Carcinogenesis, Vol 19, 1-27, Copyright © 1998 by Oxford University Press
BT Zhu and AH Conney
Cytochrome P450 enzymes that metabolize estrogens are expressed in the
mammary gland, uterus, brain and other target tissues for estrogen action,
and this results in the formation of hydroxylated estrogens in these
tissues. Estradiol metabolites formed in target tissues at or near estrogen
receptors may either be inactive or have important biological effects, and
changes in the activities of estrogen- metabolizing enzymes in target
tissues may profoundly influence estrogen action. Although some active
estrogen metabolites exert hormonal effects in target tissues by
interaction with the classical estrogen receptor, other metabolites appear
to elicit unique biological responses that are not associated with
activation of this receptor. Therefore, some of the many actions of
estradiol may not be caused by estradiol per se, but may result from the
formation of active estrogen metabolite(s) which function as local
mediators or may activate their own unique receptors or effectors. This is
an important area in need of more research. The present paper represents a
review of the literature and perspectives by the authors on the functional
role of estrogen metabolism in target tissues.
REVIEWS
Functional role of estrogen metabolism in target cells: review and perspectives
Department of Chemical Biology, College of Pharmacy, Rutgers-The State University of New Jersey, Piscataway 08854-8020, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. W. Bell, B. W. Brannigan, K. Matsuo, D. M. Finkelstein, R. Sordella, J. Settleman, T. Mitsudomi, and D. A. Haber Increased Prevalence of EGFR-Mutant Lung Cancer in Women and in East Asian Populations: Analysis of Estrogen-Related Polymorphisms Clin. Cancer Res., July 1, 2008; 14(13): 4079 - 4084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Deming, W. Zheng, W.-H. Xu, Q. Cai, Z. Ruan, Y.-B. Xiang, and X.-O. Shu UGT1A1 Genetic Polymorphisms, Endogenous Estrogen Exposure, Soy Food Intake, and Endometrial Cancer Risk Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 563 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Salih, S. A. Salama, M. Jamaluddin, A. A. Fadl, L. J. Blok, C. W. Burger, M. Nagamani, and A. Al-Hendy Progesterone-Mediated Regulation of Catechol-O-Methyl Transferase Expression in Endometrial Cancer Cells Reproductive Sciences, February 1, 2008; 15(2): 210 - 220. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Lehmann, L. Jiang, and J. Wagner Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured MCF-7 cells Carcinogenesis, February 1, 2008; 29(2): 363 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kato, A. Sadarangani, S. Lange, M. Villalon, J. Branes, J. J Brosens, G. I Owen, and M. Cuello The oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium Endocr. Relat. Cancer, June 1, 2007; 14(2): 351 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. T. Zhu, G.-Z. Han, J.-Y. Shim, Y. Wen, and X.-R. Jiang Quantitative Structure-Activity Relationship of Various Endogenous Estrogen Metabolites for Human Estrogen Receptor {alpha} and {beta} Subtypes: Insights into the Structural Determinants Favoring a Differential Subtype Binding Endocrinology, September 1, 2006; 147(9): 4132 - 4150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, K. W. Lee, F. L. Chan, S. Chen, and L. K. Leung The Red Wine Polyphenol Resveratrol Displays Bilevel Inhibition on Aromatase in Breast Cancer Cells Toxicol. Sci., July 1, 2006; 92(1): 71 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mesia-Vela, R. I. Sanchez, K. R. Reuhl, A. H. Conney, and F. C. Kauffman Phenobarbital Treatment Inhibits the Formation of Estradiol-Dependent Mammary Tumors in the August-Copenhagen Irish Rat J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 590 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. King Heiden, M. J. Carvan III, and R. J. Hutz Inhibition of Follicular Development, Vitellogenesis, and Serum 17{beta}-Estradiol Concentrations in Zebrafish Following Chronic, Sublethal Dietary Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Toxicol. Sci., April 1, 2006; 90(2): 490 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Cribb, M. J. Knight, D. Dryer, J. Guernsey, K. Hender, M. Tesch, and T. M. Saleh Role of polymorphic human cytochrome p450 enzymes in estrone oxidation. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 551 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Masi, L. C. Hawkley, J. D. Berry, and J. T. Cacioppo Estrogen Metabolites and Systolic Blood Pressure in a Population-Based Sample of Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1015 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. E. Lin, S.-C. Chien, P.-C. Hsu, and L.-A. Li Mechanistic Study of Polychlorinated Biphenyl 126-Induced CYP11B1 and CYP11B2 Up-Regulation Endocrinology, March 1, 2006; 147(3): 1536 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tanaka, M. Sasaki, H. Shiina, T. Tokizane, M. Deguchi, H. Hirata, Y. Hinoda, N. Okayama, Y. Suehiro, S. Urakami, et al. Catechol-O-methyltransferase Gene Polymorphisms in Benign Prostatic Hyperplasia and Sporadic Prostate Cancer. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 238 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Balthazart, M. Baillien, and G. F. Ball Rapid Control of Brain Aromatase Activity by Glutamatergic Inputs Endocrinology, January 1, 2006; 147(1): 359 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Weiss, N. S. Weiss, C. M. Ulrich, J. A. Doherty, L. F. Voigt, and C. Chen Interindividual Variation in Nucleotide Excision Repair Genes and Risk of Endometrial Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2524 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wellejus, A. Olsen, A. Tjonneland, B. L. Thomsen, K. Overvad, and S. Loft Urinary Hydroxyestrogens and Breast Cancer Risk among Postmenopausal Women: A Prospective Study Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2137 - 2142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Starr, C. Chen, D. R. Doody, L. Hsu, S. Ricks, N. S. Weiss, and S. M. Schwartz Risk of Testicular Germ Cell Cancer in Relation to Variation in Maternal and Offspring Cytochrome P450 Genes Involved in Catechol Estrogen Metabolism Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2183 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Reed, K. S. Peterson, H. J. Smith, J. C. Gray, D. K. Sullivan, M. S. Mayo, J. A. Crowell, and A. Hurwitz A Phase I Study of Indole-3-Carbinol in Women: Tolerability and Effects Cancer Epidemiol. Biomarkers Prev., August 1, 2005; 14(8): 1953 - 1960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Le Marchand, T. Donlon, L. N. Kolonel, B. E. Henderson, and L. R. Wilkens Estrogen Metabolism-Related Genes and Breast Cancer Risk: The Multiethnic Cohort Study Cancer Epidemiol. Biomarkers Prev., August 1, 2005; 14(8): 1998 - 2003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-J. Liu, W. J. Lee, and B. T. Zhu Selective Insensitivity of ZR-75-1 Human Breast Cancer Cells to 2-Methoxyestradiol: Evidence for Type II 17{beta}-Hydroxysteroid Dehydrogenase as the Underlying Cause Cancer Res., July 1, 2005; 65(13): 5802 - 5811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C S A Markides and J G Liehr Specific binding of 4-hydroxyestradiol to mouse uterine protein: evidence of a physiological role for 4-hydroxyestradiol J. Endocrinol., May 1, 2005; 185(2): 235 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Duell and E. A. Holly Reproductive and Menstrual Risk Factors for Pancreatic Cancer: A Population-based Study of San Francisco Bay Area Women Am. J. Epidemiol., April 15, 2005; 161(8): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kisselev, W.-H. Schunck, I. Roots, and D. Schwarz Association of CYP1A1 Polymorphisms with Differential Metabolic Activation of 17{beta}-Estradiol and Estrone Cancer Res., April 1, 2005; 65(7): 2972 - 2978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Doherty, N. S. Weiss, R. J. Freeman, D. A. Dightman, P. J. Thornton, J. R. Houck, L. F. Voigt, M. A. Rossing, S. M. Schwartz, and C. Chen Genetic Factors in Catechol Estrogen Metabolism in Relation to the Risk of Endometrial Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 357 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bandiera, S. Weidlich, V. Harth, P. Broede, Y. Ko, and T. Friedberg Proteasomal Degradation of Human CYP1B1: Effect of the Asn453Ser Polymorphism on the Post-Translational Regulation of CYP1B1 Expression Mol. Pharmacol., February 1, 2005; 67(2): 435 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Z. Han, Z.-J. Liu, K. Shimoi, and B. T. Zhu Synergism between the Anticancer Actions of 2-Methoxyestradiol and Microtubule-Disrupting Agents in Human Breast Cancer Cancer Res., January 15, 2005; 65(2): 387 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, E. K. Jackson, D. G. Gillespie, M. Rosselli, F. Barchiesi, A. Krust, H. Keller, L. C. Zacharia, and B. Imthurn Cytochromes 1A1/1B1- and Catechol-O-Methyltransferase-Derived Metabolites Mediate Estradiol-Induced Antimitogenesis in Human Cardiac Fibroblast J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. CAVALIERI and E. G. ROGAN A Unifying Mechanism in the Initiation of Cancer and Other Diseases by Catechol Quinones Ann. N.Y. Acad. Sci., December 1, 2004; 1028(1): 247 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Ji, C. Aoyama, Y.-D. Nien, P. I. Liu, P. K. Chen, L. Chang, F. Z. Stanczyk, and A. Stolz Selective Loss of AKR1C1 and AKR1C2 in Breast Cancer and Their Potential Effect on Progesterone Signaling Cancer Res., October 15, 2004; 64(20): 7610 - 7617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lepine, O. Bernard, M. Plante, B. Tetu, G. Pelletier, F. Labrie, A. Belanger, and C. Guillemette Specificity and Regioselectivity of the Conjugation of Estradiol, Estrone, and Their Catecholestrogen and Methoxyestrogen Metabolites by Human Uridine Diphospho-glucuronosyltransferases Expressed in Endometrium J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5222 - 5232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-H. Chen, Y.-J. Hurh, H.-K. Na, J.-H. Kim, Y.-J. Chun, D.-H. Kim, K.-S. Kang, M.-H. Cho, and Y.-J. Surh Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells Carcinogenesis, October 1, 2004; 25(10): 2005 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Raeside, H. L. Christie, R. L. Renaud, R. O. Waelchli, and K. J. Betteridge Estrogen Metabolism in the Equine Conceptus and Endometrium During Early Pregnancy in Relation to Estrogen Concentrations in Yolk-Sac Fluid Biol Reprod, October 1, 2004; 71(4): 1120 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Lee and B. T. Zhu NADPH-DEPENDENT FORMATION OF POLAR AND NONPOLAR ESTROGEN METABOLITES FOLLOWING INCUBATIONS OF 17{beta}-ESTRADIOL WITH HUMAN LIVER MICROSOMES Drug Metab. Dispos., August 1, 2004; 32(8): 876 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, E. K. Jackson, D. G. Gillespie, L. C. Zacharia, and B. Imthurn Catecholamines Block the Antimitogenic Effect of Estradiol on Human Coronary Artery Smooth Muscle Cells J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3922 - 3931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Atkinson, J. W. Lampe, S. S. Tworoger, C. M. Ulrich, D. Bowen, M. L. Irwin, R. S. Schwartz, B. K. Rajan, Y. Yasui, J. D. Potter, et al. Effects of a Moderate Intensity Exercise Intervention on Estrogen Metabolism in Postmenopausal Women Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 868 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mizutani, T. Okada, S. Shibutani, E. Sonoda, H. Hochegger, C. Nishigori, Y. Miyachi, S. Takeda, and M. Yamazoe Extensive Chromosomal Breaks Are Induced by Tamoxifen and Estrogen in DNA Repair-Deficient Cells Cancer Res., May 1, 2004; 64(9): 3144 - 3147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. McGrath, S. E. Hankinson, L. Arbeitman, G. A. Colditz, D. J. Hunter, and I. De Vivo Cytochrome P450 1B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility Carcinogenesis, April 1, 2004; 25(4): 559 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Eriksson, S. Skrtic, A. Niklason, L. M. Hulten, O. Wiklund, T. Hedner, and C. Ohlsson Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population Eur. Heart J., March 1, 2004; 25(5): 386 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Brooks, W. E Ward, J. E Lewis, J. Hilditch, L. Nickell, E. Wong, and L. U Thompson Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy Am. J. Clinical Nutrition, February 1, 2004; 79(2): 318 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Duguay, M. McGrath, J. Lepine, J.-F. Gagne, S. E. Hankinson, G. A. Colditz, D. J. Hunter, M. Plante, B. Tetu, A. Belanger, et al. The Functional UGT1A1 Promoter Polymorphism Decreases Endometrial Cancer Risk Cancer Res., February 1, 2004; 64(3): 1202 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, S. P. Tofovic, and E. K. Jackson Cardiovascular Pharmacology of Estradiol Metabolites J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 403 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-M. Li, R. Todorovic, P. Devanesan, S. Higginbotham, H. Kofeler, R. Ramanathan, M. L. Gross, E. G. Rogan, and E. L. Cavalieri Metabolism and DNA binding studies of 4-hydroxyestradiol and estradiol-3,4-quinone in vitro and in female ACI rat mammary gland in vivo Carcinogenesis, February 1, 2004; 25(2): 289 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Guo, X. Li, J. D. Browning Jr., G. E. Rottinghaus, D. B. Lubahn, A. Constantinou, M. Bennink, and R. S. MacDonald Dietary Soy Isoflavones and Estrone Protect Ovariectomized ER{alpha}KO and Wild-Type Mice from Carcinogen-Induced Colon Cancer J. Nutr., January 1, 2004; 134(1): 179 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Conney Enzyme Induction and Dietary Chemicals as Approaches to Cancer Chemoprevention: The Seventh DeWitt S. Goodman Lecture Cancer Res., November 1, 2003; 63(21): 7005 - 7031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Wu, C.-C. Tseng, D. Van Den Berg, and M. C. Yu Tea Intake, COMT Genotype, and Breast Cancer in Asian-American Women Cancer Res., November 1, 2003; 63(21): 7526 - 7529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lee, A. H. Conney, and B. T. Zhu Human Cytochrome P450 3A7 Has a Distinct High Catalytic Activity for the 16{alpha}-Hydroxylation of Estrone but not 17{beta}-Estradiol Cancer Res., October 1, 2003; 63(19): 6532 - 6536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Riley, S. Duensing, T. Brake, K. Munger, P. F. Lambert, and J. M. Arbeit Dissection of Human Papillomavirus E6 and E7 Function in Transgenic Mouse Models of Cervical Carcinogenesis Cancer Res., August 15, 2003; 63(16): 4862 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lee, M. X. Cai, P. E. Thomas, A. H. Conney, and B. T. Zhu Characterization of the Oxidative Metabolites of 17{beta}-Estradiol and Estrone Formed by 15 Selectively Expressed Human Cytochrome P450 Isoforms Endocrinology, August 1, 2003; 144(8): 3382 - 3398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Bianco, G. Perry, M. A. Smith, D. J. Templeton, and M. M. Montano Functional Implications of Antiestrogen Induction of Quinone Reductase: Inhibition of Estrogen-Induced Deoxyribonucleic Acid Damage Mol. Endocrinol., July 1, 2003; 17(7): 1344 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Prokai, K. Prokai-Tatrai, P. Perjesi, A. D. Zharikova, and J. W. Simpkins QUINOL-BASED METABOLIC CYCLE FOR ESTROGENS IN RAT LIVER MICROSOMES Drug Metab. Dispos., June 1, 2003; 31(6): 701 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Samuni, E. Y. Chuang, M. C. Krishna, W. Stein, W. DeGraff, A. Russo, and J. B. Mitchell Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants PNAS, April 29, 2003; 100(9): 5390 - 5395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Barbier, L. Villeneuve, V. Bocher, C. Fontaine, I. P. Torra, C. Duhem, V. Kosykh, J.-C. Fruchart, C. Guillemette, and B. Staels The UDP-glucuronosyltransferase 1A9 Enzyme Is a Peroxisome Proliferator-activated Receptor alpha and gamma Target Gene J. Biol. Chem., April 11, 2003; 278(16): 13975 - 13983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. F. Kadlubar, G. S. Berkowitz, R. R. Delongchamp, C. Wang, B. L. Green, G. Tang, J. Lamba, E. Schuetz, and M. S. Wolff The CYP3A4*1B Variant Is Related to the Onset of Puberty, A Known Risk Factor for the Development of Breast Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2003; 12(4): 327 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Sibonga, S. Lotinun, G. L. Evans, V. S. Pribluda, S. J. Green, and R. T. Turner Dose-Response Effects of 2-Methoxyestradiol on Estrogen Target Tissues in the Ovariectomized Rat Endocrinology, March 1, 2003; 144(3): 785 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Dubey, D. G. Gillespie, L. C. Zacharia, F. Barchiesi, B. Imthurn, and E. K. Jackson CYP450- and COMT-Derived Estradiol Metabolites Inhibit Activity of Human Coronary Artery SMCs Hypertension, March 1, 2003; 41(3): 807 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Rasmussen, T. K. Andreassen, S. N. Pedersen, L. T. M. Van der Ven, P. Bjerregaard, and B. Korsgaard Effects of waterborne exposure of octylphenol and oestrogen on pregnant viviparous eelpout (Zoarces viviparus) and her embryos in ovario J. Exp. Biol., December 15, 2002; 205(24): 3857 - 3876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lippman and W. K. Hong Cancer Prevention Science and Practice Cancer Res., September 15, 2002; 62(18): 5119 - 5125. [Full Text] [PDF]
|
|
|
|
|
|
S. Mesia-Vela, R. I. Sanchez, J. J. Li, S. A. Li, A. H. Conney, and F. C. Kauffman Catechol estrogen formation in liver microsomes from female ACI and Sprague-Dawley rats: comparison of 2- and 4-hydroxylation revisited Carcinogenesis, August 1, 2002; 23(8): 1369 - 1372. |