Modulation of the hepatic expression of the estrogen-regulated mRNA stabilizing factor by estrogenic and antiestrogenic nonsteroidal xenobiotics.
Estrogen-mediated accumulation of apolipoprotein II (apoII) mRNA in the avian liver is due, in part, to its stabilization. This stabilization appears to be due to the estrogen-regulated mRNA stabilizing factor (E-RmRNASF) that is expressed in response to estrogen. The E-RmRNASF protects the mRNA from targeted endonucleolytic degradation (Ratnasabapathy, Cell Mol Biol Res 41: 583-594, 1995). To determine whether certain environmental xenobiotics altered the expression of the gene encoding E-RmRNASF by mimicking estrogen, roosters were given estrogen, tamoxifen, clomiphene, hexachlorophene, lindane, rotenone, chlordecone, dichlorodiphenyltrichloroethane (DDT); Araclor, methoxychlor, dieldrin, toxaphene, or bisphenol-A parenterally. Uniformly radiolabeled, capped, and polyadenylated apoII mRNA, incubated in vitro in the presence of liver cytosolic extracts from birds that received estrogen, tamoxifen, hexachlorophene, chlordecone, or Araclor, remained stable, indicating that these agents were estrogenic and stimulated the expression of E-RmRNASF. However, the same mRNA was degraded in similar extracts from control roosters and those treated with clomiphene, DDT, methoxychlor, dieldrin, rotenone, toxaphene, lindane, or bisphenol-A. To determine whether the latter agents were antiestrogenic, roosters were given a 1:5 molar combination of estrogen and each of the xenobiotics. ApoII mRNA showed degradation in liver extracts from roosters that received clomiphene, toxaphene, or bisphenol-A, indicating that these agents prevented estrogenic stimulation of expression of the E-RmRNASF and were antiestrogenic. However, the rest of the xenobiotics failed to antagonize estrogenic stimulation of E-RmRNASF gene expression. These results set a precedent in showing the estrogenic and antiestrogenic effects in vivo of environmental xenobiotics on the expression of a regulatory protein involved in estrogen-mediated mRNA stabilization.
Ratnasabapathy
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Division of Pharmacology, Toxicology and Medicinal Chemistry, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, NY 11201, U.S.A.
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D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics*; D002273:Carcinogens / Q000494:pharmacology; D002645:Chickens; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015262:Xenobiotics / Q000494:pharmacology*
D016633:Apolipoprotein A-II; D002273:Carcinogens; D004965:Estrogen Antagonists; D004967:Estrogens; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015262:Xenobiotics