Estrogen exposure and metabolic gene expression.Ansell PJ, Espinosa-Nicholas C, Curran EM, Judy BM, Philips BJ, Hannink M, Lubahn DB. 2004. In vitro and in vivo regulation of antioxidant response element-dependent gene expression by estrogens. Endocrinology 145:311-317. Exposure to chemicals that cause oxidative stress can contribute to the development of many diseases, including cancer. Many times, however, the metabolism of such chemicals has proven to be effective in modulating the degree of oxidative damage. In this paper, NIEHS grantee An individual to whom a transfer or conveyance of property is made. In a case involving the sale of land, the buyer is commonly known as the grantee. grantee n. Dennis B. Lubahn and colleagues from the University of Missouri-Columbia explore how estrogen exposure affects enzyme expression during phase II of metabolism. Understanding how estrogens regulate phase II detoxification phase II detoxification, n the second step in the two-step process for neutralizing toxic chemicals in the liver, during which several enzymes combine with the toxins to convert them into neutral substances or to make them easier to eliminate from the body. enzymes is important in explaining why estrogen exposure increases the risk of developing breast, ovarian, and uterine cancers. The metabolism of many chemicals involves two distinct phases, each with characteristic enzymes. Phase I enzymes oxidize oxidize /ox·i·dize/ (ok´si-diz) to cause to combine with oxygen or to remove hydrogen. ox·i·dize v. 1. To combine with oxygen; change into an oxide. 2. many chemicals, thereby forming intermediates. Phase II detoxification enzymes (such as glutathione-S-transferases and quinone quinone Any member of a class of cyclic organic compounds comprising a six-membered unsaturated ring (see saturation) to which two oxygen atoms are bonded as carbonyl groups (−C=O; see functional group). reductase reductase /re·duc·tase/ (-tas) a term used in the names of some of the oxidoreductases, usually specifically those catalyzing reactions important solely for reduction of a metabolite. ), which are responsible for metabolizing the products of phase I metabolic reactions, degrade these reactive intermediates by conjugation conjugation, in genetics conjugation, in genetics: see recombination. conjugation, in grammar conjugation: see inflection. or reduction reactions, thereby protecting cells from oxidative DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. damage. Phase II enzyme expression is regulated by a DNA sequence known as the antioxidant response element. The Missouri researchers sought to determine whether and how 17[beta]-estradiol regulates gene expression that depends upon the antioxidant response element. Their results indicate that 17[beta]-estradiol repressed glutathione-S-transferase gene expression. Additionally, glutathione-S-transferase and quinone reductase activities in the mouse uterus were significantly lowered in a dose-dependent manner following 17[beta]-estradiol exposure. The researchers conclude that 17[beta]-estradiol and other estrogens can downregulate phase II enzyme activities in the uterus, thus potentially slowing the metabolism of reactive intermediates. This repression may increase cellular oxidative DNA damage that ultimately can result in the formation of cancer in estrogen-responsive tissues such as the breast and female reproductive organs. |
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