Development of an ER action indicator mouse for the study of estrogens, selective ER modulators (SERMs), and Xenobiotics

Endocrinology
S C NagelD P McDonnell

Abstract

We have developed a transgenic mouse that functions as a reporter of ER activity, termed ER action indicator (ERIN), by incorporating a transgene with an estrogen-responsive promoter (three copies of the vitellogenin estrogen response element with a minimal thymidine kinase promoter) linked to the reporter gene beta-galactosidase. Evaluation of ER activity in female ERIN mice demonstrated estrogen-inducible expression of the reporter gene in the uterus, pituitary, and hypothalamus; established targets of estrogen action. Importantly, we also identified ER activity in a number of nonclassical estrogen target tissues, including kidney, liver, adrenal, and thyroid gland. ERIN provides a system to measure the same end point (transgene regulation) in different target tissues, permitting separation of the contributions of cell- and promoter-specific factors in determining ER pharmacology. In this regard we observed that on this specific promoter the pituitary gland was 25-fold more sensitive than the uterus to the estrogen diethylstilbestrol, implying the existence of cell-specific factors that influence ligand sensitivity. Our studies also identified considerable difference in the efficacy and potency of ER ligands in the uterus whe...Continue Reading

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Citations

Mar 16, 2012·Endocrine Reviews·Laura N VandenbergJohn Peterson Myers
Sep 18, 2007·Molecular Endocrinology·Carolyn D DuSellDonald P McDonnell
Jul 5, 2003·Environmental Health Perspectives·Kembra L HowdeshellWade V Welshons
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Jun 16, 2004·Molecular and Cellular Endocrinology·Romain GuyotBrigitte Le Magueresse-Battistoni
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Sep 17, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Diego Di LorenzoAdriana Maggi

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