Superfund Research Program
Estrogen Receptor-Arylhydrocarbon Receptor Interactions in the CNS
Project Leader: Gloria V. Callard
Grant Number: P42ES007381
Funding Period: 2000-2012
Several endocrine disruptors were tested in zebrafish embryos. Results are consistent with the presence of estrogen response elements (EREs) and xenobiotic response elements (XREs) in the cyp19B and cyp19A genes, respectively. A PCR cloning strategy was used to isolate three ER genes and design gene-specific primers and probes.
Expression patterns of P450aromB/A and ERa/bA/bB mRNAs during development and in specific tissues of adult and aging fish have been documented.
Microscopic and morphometric techniques failed to identify neuroanatomic defects due to early estrogen exposure, although more recent experiments show upregulation by estrogen of GAP43 and alpha tubulin.
Early results suggest that effects on estrogen biosynthesis can occur at lower concentrations in ovary than in brain. Results of a gene-specific RT-PCR assay surprisingly show that Nur77 itself is upregulated by estrogen and xenoestrogens in embryos and adult brain, indicative of an additional mechanism for amplifying neuroestrogen effects in the developing CNS.