Ratnasabapathy, R; Deangelis, D; Raje, R
Estrogen regulates the expression of apolipoprotein(apo)II mRNA in the avian liver at transcriptional and post-transcriptional levels. The stabilization of apoII mRNA appears to be due in part 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, 1995, Cell. Mol. Biol. Res., 41, 583-594). The hepatic expression of E-RmRNASF is modulated by certain estrogenic and antiestrogenic nonsteroidal environmental xenobiotics (Ratnasabapathy et al., Biochem. Pharmacol., in press). To determine whether the expression of the gene encoding apolipoprotein II was also subject to modulation by environmental xenobiotics that mimic estrogen, roosters were given estrogen, tamoxifen, clomiphene, hexachlorophene, lindane, rotenone, chlordecone, DDT, araclor, methoxychlor, dieldrin, toxaphene or bisphenol-A parenterally. The apolipoprotein II mRNA levels in rooster livers were determined by RT-PCR. ApoII mRNA expression was stimulated in the livers of birds who received estrogen, tamoxifen, hexachlorophene, chlordecone or araclor, indicating that these agents were estrogenic. However, a lack of induction of apoII mRNA expression in the liver was seen with control roosters and those treated with clomiphene, DDT, methoxychlor, dieldrin, rotenone, toxaphene, lindane or bisphenol-A. To determine whether the latter agents were anti-estrogenic, roosters were given a 1:5 molar combination of estrogen and each of the xenobiotics. Estrogenic induction of apoII mRNA in the liver was prevented by clomiphene, toxaphene or bisphenol-A, indicating that these agents were anti-estrogenic. However, the rest of the xenobiotics failed to antagonize estrogenic stimulation of apoII gene expression.
