The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat

Reprod Toxicol. 2013 Apr;36:71-7. doi: 10.1016/j.reprotox.2012.12.001. Epub 2012 Dec 20.

Abstract

Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect. To further characterize this potentiation, we evaluated the effect of co-exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs. Changes in uterine weight, epithelial cell growth, and estrogen-sensitive gene expression were assessed. TCS expectedly enhanced the uterotrophic response to EE, however at significantly lower doses of EE. Similarly, TCS increased the EE-induced stimulation of epithelial cell height following cotreatment. Cotreatment also enhanced the estrogen-induced change in gene expression, which was reversed with an ER antagonist. Furthermore, the TCS-induced potentiation was independent of ER activation, as no effects were observed in the ER TA assay.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / antagonists & inhibitors
  • Anti-Bacterial Agents / toxicity
  • Cell Shape / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / chemistry
  • Endocrine Disruptors / toxicity*
  • Estrogen Antagonists / pharmacology
  • Estrogen Antagonists / therapeutic use
  • Estrogen Replacement Therapy / adverse effects
  • Estrogens / administration & dosage
  • Estrogens / adverse effects
  • Estrogens / agonists*
  • Estrogens / pharmacology
  • Ethinyl Estradiol / adverse effects
  • Ethinyl Estradiol / agonists*
  • Ethinyl Estradiol / antagonists & inhibitors
  • Ethinyl Estradiol / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Organ Size / drug effects
  • Precancerous Conditions / chemically induced*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Precancerous Conditions / prevention & control
  • Random Allocation
  • Rats
  • Receptors, Estrogen / agonists
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Triclosan / administration & dosage
  • Triclosan / antagonists & inhibitors
  • Triclosan / toxicity*
  • Uterus / drug effects*
  • Uterus / growth & development
  • Uterus / metabolism
  • Uterus / pathology
  • Weaning

Substances

  • Anti-Bacterial Agents
  • Endocrine Disruptors
  • Estrogen Antagonists
  • Estrogens
  • Receptors, Estrogen
  • Ethinyl Estradiol
  • Triclosan