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COMPARISON OF THE EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS (EDCS) ON AROMATASE (CYP19) ACTIVITY IN RATS AND FISH
Impact/Purpose:
The specific objectives of these studies are (1) to determine if endocrine disrupting chemicals (EDCs) alter steroid concentrations in rats and fish through a direct effect on aromatase (CYP19) activity; (2) to compare the dose response (e.g., sensitivity) of each species to perturbation by chlorotriazines and alkylphenols; and (3) to provide comparative toxicological data for across species extrapolation for this MOA.
Description:
Aromatase, a product of the CYP19 gene, is an important enzyme during steroidogenesis that catalyzes the conversion of androstenedione and testosterone to estrone and estradiol. It is expressed in gonadal and extragonadal tissues in all vertebrates, and is critical for the homeostasis balance between the sex steroids in male and females. The regulation of aromatase expression is tissue-specific and varies during different stages of the life cycle. Aromatase is essential during perinatal development for sexual differentiation of the male brain and for the regulation of gonadal steroids in the ovary and testes during adulthood. Aromatase activity in extragonadal tissues is important for the regulation of local estrogen concentrations in both young and aging vertebrates. There are strong indications that alterations in aromatase activity is associated with disrupted reproductive function and/or disease in laboratory animals, humans and wildlife. These studies will compare the effects of endocrine disrupting chemicals (EDCs) on aromatase (CYP 19) activity in rats and fish. Specifically, these studies will test the hypothesis that EDCs, such as the alkylphenols and chlorotriazines, modulate estrogen concentrations in rats and fish through this common mode of action (MOA).