MODULATION OF THE HEPATIC EXPRESSION OF THE ESTROGEN-REGULATED MESSENGER-RNA STABILIZING FACTOR BY ESTROGENIC AND ANTIESTROGENIC NONSTEROIDAL XENOBIOTICS

Estrogen-mediated accumulation of apolipoprotein II (apoII) mRNA in th e avian liver is due, in part, to its stabilization. This stabilizatio n appears to be due to the estrogen-regulated mRNA stabilizing factor (E-RmRNASF) that is expressed in response to estrogen. The E-RmRNASF p rotects the mRNA from targeted endonucleolytic degradation (Ratnasabap athy, Cell Mol Biol Res 41: 583-594, 1995). To determine whether certa in environmental xenobiotics altered the expression of the gene encodi ng E-RmRNASF by mimicking estrogen, roosters were given estrogen, tamo xifen, clomiphene, hexachlorophene, lindane, rotenone, chlorde-cone co ne, dichlorodiphenyltrichloroethane (DDT), Araclor, methoxychlor, diel drin, toxaphene, or bisphenol-A parenterally. Uniformly radiolabeled, capped, and polyadenylated apoII mRNA, incubated in vitro in the prese nce of liver cytosolic extracts from birds that received estrogen, tam oxifen, hexachlorophene, chlordecone, or Araclor, remained stable, ind icating that these agents were estrogenic and stimulated the expressio n of E-RmRNASF. However, the same mRNA was degraded in similar extract s from control roosters and those treated with clomiphene, DDT, methox ychlor, dieldrin, rotenone, toxaphene, lindane, or bisphenol-A. To det ermine whether the latter agents were antiestrogenic, roosters were gi ven a 1:5 molar combination of estrogen and each of the xenobiotics. A poII mRNA showed degradation in liver extracts from roosters that rece ived clomiphene, toxaphene, or bisphenol-A, indicating that these agen ts prevented estrogenic stimulation of expression of the E-RmRNASF and were antiestrogenic. However, the rest of the xenobiotics failed to a ntagonize estrogenic stimulation of E-RmRNASF gene expression. These r esults set a precedent in showing the estrogenic and antiestrogenic ef fects in vivo of environmental xenobiotics on the expression of a regu latory protein involved in estrogen-mediated mRNA stabilization. (C) 1 997 Elsevier Science Inc.