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...

[1]  J. Corton,et al.  Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β. , 1998, Endocrinology.

[2]  J. Lehmann,et al.  Cloning and Characterization of Human Estrogen Receptor β Isoforms , 1998 .

[3]  S. Kato,et al.  A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the ligand binding domain as a putative dominant negative regular of estrogen action. , 1998, Biochemical and biophysical research communications.

[4]  K. Korach,et al.  Estrogenic responses in estrogen receptor-alpha deficient mice reveal a distinct estrogen signaling pathway. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Korach,et al.  Tissue Distribution and Quantitative Analysis of Estrogen Receptor-α (ERα) and Estrogen Receptor-β (ERβ) Messenger Ribonucleic Acid in the Wild-Type and ERα-Knockout Mouse. , 1997, Endocrinology.

[6]  S. Chu,et al.  Identification of a splice variant of the rat estrogen receptor β gene , 1997, Molecular and Cellular Endocrinology.

[7]  J. Putnam,et al.  Effect of methoxychlor on implantation and embryo development in the mouse. , 1997, Reproductive toxicology.

[8]  S. Inoue,et al.  Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta. , 1997, Biochemical and biophysical research communications.

[9]  K. Korach,et al.  Promoter and species specific differential estrogen-mediated gene transcription in the uterus and cultured cells using structurally altered agonists. , 1997, Journal of molecular endocrinology.

[10]  D. Vorojeikina,et al.  Transcriptional activation of the human estrogen receptor by DDT isomers and metabolites in yeast and MCF-7 cells. , 1997, Biochemical pharmacology.

[11]  Betty C. B. Huang,et al.  Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[12]  B. J. Danzo,et al.  Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. , 1997, Environmental health perspectives.

[13]  D. Sömjen,et al.  Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo , 1996, The Journal of Steroid Biochemistry and Molecular Biology.

[14]  D. Johnson,et al.  Estradiol-chlordecone (Kepone) interactions: additive effect of combinations for uterotropic and embryo implantation functions. , 1996, Toxicology letters.

[15]  S. Laws,et al.  Methoxychlor mimics the action of 17 beta-estradiol on induction of uterine epidermal growth factor receptors in immature female rats. , 1996, Reproductive toxicology.

[16]  A. Rourke,et al.  Estradiol or methoxychlor stimulates estrogen receptor (ER) expression in uteri. , 1996, Reproductive toxicology.

[17]  J. Gustafsson,et al.  Cloning of a novel receptor expressed in rat prostate and ovary. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Karas,et al.  Human vascular smooth muscle cells express an estrogen receptor isoform , 1995, FEBS letters.

[19]  K. Korach,et al.  Analysis of transcription and estrogen insensitivity in the female mouse after targeted disruption of the estrogen receptor gene. , 1995, Molecular endocrinology.

[20]  R. Newbold.  Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens. , 1995, Environmental health perspectives.

[21]  L. Gray,et al.  Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist , 1995, Nature.

[22]  M. Shupnik,et al.  Estrogen regulates the expression of several different estrogen receptor mRNA isoforms in rat pituitary. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[23]  W. Welshons,et al.  Estrogenic pesticides: binding relative to estradiol in MCF-7 cells and effects of exposure during fetal life on subsequent territorial behaviour in male mice. , 1995, Toxicology letters.

[24]  S. Safe,et al.  Environmental and dietary estrogens and human health: is there a problem? , 1995, Environmental health perspectives.

[25]  Kazuto Ito,et al.  Synergistic effects of estrogen and androgen on the prostate: Effects of estrogen on androgen‐and estrogen‐receptors, BrdU uptake, immunohistochemical study of AR, and responses to antiandrogens , 1995, The Prostate.

[26]  A. Cummings,et al.  Mechanisms of the stimulation of rat uterine peroxidase activity by methoxychlor. , 1994, Reproductive toxicology.

[27]  K. Korach,et al.  Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  L. Walters,et al.  Purified methoxychlor stimulates the reproductive tract in immature female mice. , 1993, Reproductive toxicology.

[29]  M. Tetzlaff,et al.  Identification of an isoform of the estrogen receptor messenger RNA lacking exon four and present in the brain. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Ray,et al.  Subcellular action of estradiol-17 beta in a freshwater prawn Macrobrachium rosenbergii. , 1993, General and comparative endocrinology.

[31]  C. Teng,et al.  Estrogen response module of the mouse lactoferrin gene contains overlapping chicken ovalbumin upstream promoter transcription factor and estrogen receptor-binding elements. , 1992, Molecular Endocrinology.

[32]  A. Wakeling,et al.  A potent specific pure antiestrogen with clinical potential. , 1991, Cancer research.

[33]  J. Blume,et al.  Ribosome loading, but not protein synthesis, is required for estrogen stabilization of Xenopus laevis vitellogenin mRNA. , 1989, Nucleic acids research.

[34]  C. Teng,et al.  Lactotransferrin is the major estrogen inducible protein of mouse uterine secretions. , 1987, The Journal of biological chemistry.

[35]  D. Kupfer,et al.  Metabolic activation of pesticides with proestrogenic activity. , 1987, Federation proceedings.

[36]  G. Bogliolo,et al.  Cytotoxic effect of dose and schedule on normal murine hematopoietic progenitor cells following the administration of 4'-deoxydoxorubicin. , 1984, British Journal of Cancer.

[37]  R. Muccitelli,et al.  Interactions of methoxychlor, methoxychlor base-soluble contaminant, and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane with rat uterine estrogen receptor. , 1978, Journal of toxicology and environmental health.

[38]  W. Heinrichs,et al.  DDT homologues: estrogen-like effects on the vagina, uterus and pituitary of the rat. , 1972, Endocrinology.

[39]  J. Bitman,et al.  Estrogenic activity of DDT analogs and polychlorinated biphenyls. , 1970, Journal of agricultural and food chemistry.

[40]  A. Conney,et al.  Estrogenic action of DDT and its analogs. , 1969, Toxicology and applied pharmacology.

[41]  K. Gaido,et al.  Differential interaction of the methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane with estrogen receptors alpha and beta. , 1999, Endocrinology.

[42]  J. Corton,et al.  Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. , 1998, Endocrinology.

[43]  K. Grandien,et al.  Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors a and b , 1997 .

[44]  J. Gustafsson,et al.  Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. , 1997, Endocrinology.

[45]  M. Longnecker,et al.  The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health. , 1997, Annual review of public health.

[46]  J. Gustafsson,et al.  Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. , 1997, Endocrinology.

[47]  J. Polman,et al.  ER beta: identification and characterization of a novel human estrogen receptor. , 1996, FEBS letters.

[48]  C. Wink,et al.  Response of adult murine uterine epithelium to 50% methoxychlor. , 1994, Reproductive toxicology.

[49]  P. Han,et al.  Modulation of hepatic glucose-6-phosphate dehydrogenase activity in male and female rats by estrogen. , 1989, Life sciences.

[50]  P. Guzelian.  Comparative toxicology of chlordecone (Kepone) in humans and experimental animals. , 1982, Annual review of pharmacology and toxicology.

[51]  R. Muccitelli,et al.  Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites. Role of hepatic mono-oxygenase in methoxychlor activation. , 1978, Biochemical pharmacology.

[52]  R. J. Gellert,et al.  Kepone, mirex, dieldrin, and aldrin: estrogenic activity and the induction of persistent vaginal estrus and anovulation in rats following neonatal treatment. , 1978, Environmental research.

[53]  Printed in U.S.A. Copyright © 1998 by The Endocrine Society Differential Spatiotemporal Regulation of Lactoferrin and Progesterone Receptor Genes in the Mouse Uterus by Primary Estrogen, Catechol Estrogen, and Xenoestrogen* , 2022 .