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Endocrinology Vol. 140, No. 8 3526-3533
Copyright © 1999 by The Endocrine Society

ARTICLES

Methoxychlor Stimulates Estrogen-Responsive Messenger Ribonucleic Acids in Mouse Uterus through a Non-Estrogen Receptor (Non-ER){alpha} and Non-ERß Mechanism1

Debjani Ghosh, Julia A. Taylor, Jonathan A. Green and Dennis B. Lubahn

Departments of Biochemistry and Child Health (D.G., J.A.T., D.B.L.) and Animal Sciences (J.A.G., D.B.L.), University of Missouri, Columbia, Missouri 65211

Address all correspondence and requests for reprints to: Dr. Dennis B. Lubahn, Departments of Biochemistry and Child Health, 163A Animal Science Research Center, 920 East Campus Drive, University of Missouri, Columbia, Missouri 65211. E-mail: lubahnd{at}missouri.edu

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){alpha}-knockout (ER{alpha}KO) mice were treated with Mxc or estradiol-17ß (E2) to determine whether Mxc acts via pathways that involve ER{alpha}. 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 ER{alpha}KO 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 ER{alpha}KO mouse were not suppressed by competitive pretreatment with either E2 or ICI 182,780. Fold increases in mRNA concentrations for both genes induced by Mxc were similar for WT and ER{alpha}KO mice. The results surprisingly indicate that a xenoestrogen, Mxc, can increase LF and G6PD mRNA concentrations by a mechanism that is not mediated through ER{alpha} or ERß, and acts through another pathway.




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