| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on June 30, 2003
Accepted on September 26, 2003
1 Departments of Biochemistry, and Veterinary Pathobiology, Child Health, Animal Sciences, MU Center for Phytonutrient and Phytochemical Studies, University of Missouri, Columbia, MO 65211. Present Address Department of Pharmacology and Therapeutics, Roswell Cancer Institute, Buffalo, NY 14262
* To whom correspondence should be addressed. E-mail: LubahnD{at}missouri.edu.
Understanding estrogen's regulation of phase II detoxification enzymes is important in explaining how estrogen exposure increases the risk of developing certain cancers. Phase II enzymes such as glutathione transferases (GST) and quinone reductase (QR), protect against developing chemically induced cancers by metabolizing reactive oxygen species. Phase II enzyme expression is regulated by a cis acting DNA sequence, the antioxidant response element (ARE). It has previously been reported that several antiestrogens, but not 17
-estradiol, could regulate ARE mediated gene transcription. Our goal was to determine if additional estrogenic compounds could regulate ARE-mediated gene expression both in vitro and in vivo. We discovered that physiological concentrations (10 nM) of 17-estradiol repressed GST Ya ARE dependent gene expression in vitro. Treatment with other endogenous-, anti-, xeno-, and phyto-estrogens showed that ER/ARE signaling is ligand, receptor-subtype, and cell-type specific. Additionally, GST and QR activities were significantly lowered in a dose dependent manner after 17-estradiol exposure in the uteri of mice. In conclusion, we have shown that 17-estradiol, and other estrogens, down-regulate phase II enzyme activities. We propose estrogen-mediated repression of phase II enzyme activities may increase cellular oxidative DNA damage that ultimately can result in the formation of cancer in some estrogen-responsive tissues.
This article has been cited by other articles:
 |
|
 |
|
  B. Yu, B. M. Dietz, T. Dunlap, I. Kastrati, D. D. Lantvit, C. R. Overk, P. Yao, Z. Qin, J. L. Bolton, and G. R.J. Thatcher Structural modulation of reactivity/activity in design of improved benzothiophene selective estrogen receptor modulators: induction of chemopreventive mechanisms Mol. Cancer Ther., September 1, 2007; 6(9): 2418 - 2428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Mann, D. J. Rowlands, F. Y.L. Li, P. de Winter, and R. C.M. Siow Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression Cardiovasc Res, July 15, 2007; 75(2): 261 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhou, Z. Liu, J. Wu, J.-h. Liu, S. M. Hyder, E. Antoniou, and D. B. Lubahn Identification and Characterization of Two Novel Splicing Isoforms of Human Estrogen-Related Receptor {beta} J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 569 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi and T. E. Spencer Estrogen Disruption of Neonatal Ovine Uterine Development: Effects on Gene Expression Assessed by Suppression Subtraction Hybridization Biol Reprod, October 1, 2005; 73(4): 752 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Juan, J.-J. Chen, C.-H. Chen, H. Lin, C.-F. Cheng, J.-C. Liu, M.-H. Hsieh, Y.-L. Chen, H.-H. Chao, T.-H. Chen, et al. 17{beta}-Estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1254 - H1261. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
