Modulation of the hepatic expression of the estrogen-regulated mRNA stabilizing factor by estrogenic and antiestrogenic nonsteroidal xenobiotics

Estrogen-mediated accumulation of apolipoprotein II (apoll) 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 fro...

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Published in:	Biochemical pharmacology Vol. 53; no. 10; pp. 1425 - 1434
Main Authors:	Ratnasabapathy, Ratneswaran, Tom, Meldon, Post, Carole
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 15-05-1997 Elsevier Science
Subjects:	Animals Apolipoprotein A-II - genetics apolipoprotein II Biological and medical sciences Carcinogens - pharmacology Chemical and industrial products toxicology. Toxic occupational diseases Chickens environmental toxicants estrogen Estrogen Antagonists - pharmacology Estrogens - pharmacology Gene Expression - drug effects Liver - metabolism Male Medical sciences mRNA stability pollutants RNA, Messenger - metabolism RNA-Binding Proteins - metabolism Toxicology Various organic compounds xenobiotics Xenobiotics - pharmacology estrogen apolipoprotein II xenobiotics environmental toxicants pollutants mRNA stability Stability Digestive system Toxicity Liver Antiestrogen Estrogen Pesticides Antihormone Apolipoproteins Gene expression In vitro Pollutant Messenger RNA Organochlorine compounds Animal Mechanism of action Non steroid compound Xenobiotic
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Summary:	Estrogen-mediated accumulation of apolipoprotein II (apoll) 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 apoll 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. Apoll 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.
ISSN:	0006-2952 1873-2968
DOI:	10.1016/S0006-2952(97)00084-1