Methoxychlor Stimulates Estrogen-Responsive Messenger Ribonucleic Acids in Mouse Uterus through a Non-Estrogen Receptor (Non-ER)α and Non-ERβ Mechanism.

This study examined the effects of the xenoestrogen methoxychlor (Mxc) on messenger RNA (mRNA) concentrations of two estrogen-responsive uterine genes, lactoferrin (LF) and glucose-6-phosphate dehydrogenase (G6PD). Ovariectomized wild-type (WT) and estrogen receptor (ER)α-knockout (ERαKO) mice were treated with Mxc or estradiol-17β (E2) to determine whether Mxc acts via pathways that involve ERα. In WT mice, both E2 and Mxc stimulated increases in uterine LF and G6PD mRNA concentrations in a dose-dependent manner. Competitive pretreatment with the pure antiestrogen ICI 182,780 dramatically reduced E2-stimulated increases in mRNA concentrations but had no effect on Mxc-induced effects. Competitive pretreatment with E2 had only a partially inhibitory effect on Mxc-induced responses. In the ERαKO mouse, E2 had little effect on uterine LF or G6PD mRNA concentrations, whereas Mxc stimulated marked increases in both LF and G6PD mRNAs. The Mxc-induced increases in LF and G6PD mRNAs in the ERαKO mouse were not su...

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