Abstract
The aromatic hydrocarbon receptor (AHR) mediates the toxicity of several halogenated aromatic hydrocarbons, including 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). In order to better understand the systemic endocrine disruption induced by AHR agonists, we examined the regulation of AHR by exposure to TCDD during gestation and lactation. Pregnant rats were given an oral dose of 1 μg TCDD/kg body weight or vehicle control on day 15 of gestation, and female pups sacrificed on post-natal day 21. Total RNA from ovaries, uteri, and hypothalami was immobilized on a nylon membrane and probed with a murine AHR cDNA. The gel mobility-shift assay was used to asses changes in the DNA-binding activity of AHR in vitro. Ovarian AHR mRNA and DNA-binding capability were decreased 2.1- and 1.7-fold, respectively; while in the uterus, there was a 1.3- and 1.5-fold increase in message and DNA binding. Hypothalamic mRNA for AHR showed no change, while there was a 1.7-fold increase in DNA-binding activity. Our results show that in-utero and lactational exposure to TCDD alters the expression of AHR in a tissue-specific fashion, and that this altered regulation may either be a part or a cause of the general endocrine disruption observed in these animals.
