BRAIN AROMATASE (CYP19A1B) IS A HIGHLY SENSITIVE GENE TO ESTROGENS AND XENO-ESTROGENS

摘要

Aromatase is the only enzyme responsible for the irreversible conversion of androgens into estrogens. Teleost fishes have two copies of the cyp19a1 gene that encode two isoforms of aromatase: cyp19a1a encodes ovarian aromatase, while the cyp19a1b gene encodes brain aromatase (aromatase B). We have shown that (i) aromatase B is strongly expressed in radial glial cells (RGC), that act as stem cells in mammals and fish and ii) the cyp19a1b gene is very sensitive to estrogens, through a mechanism that involves a well conserved ERE. This feature makes this gene an outstanding biomarker of xeno-estrogen exposures and we have developed and validated an in vivo assay allowing detection of estrogenic activity with a very high sensitivity. The in vivo assay is based on a transgenic zebrafish tg(cyp 19a 1b-GFP) line that expresses GFP in RGCs and we demonstrate the usefulness of the transgenic cyp19a1b-GFP as a reliable, sensitive and rapid in vivo estrogenic screening assay