Transcriptional responses in the brain, liver and gonad of Japanese ricefish (Oryzias latipes) exposed to two anti-estrogens.

The study of endocrine disruption is being increasingly conducted at the mRNA level of genes, as this approach might yield insight into the modes of action and mechanisms of toxicity. In this study, the transcriptional responses of a set of functionally relevant genes associated with the pathways of the hypothalamic-pituitary-gonadal (HPG; or HPG[L]-liver) axis of Japanese ricefish were examined after treatment with two model anti-estrogens, letrozole (LET) and tamoxifen (TAM), at three concentrations (30, 100 and 300μg/L) for 72h. The results showed that LET and TAM produced distinct expression profiles in a complex tissue- and gender-specific manner, confirming that they exert their anti-estrogenic effects via different molecular mechanisms. For example, the transcriptional levels of hepatic vitellogenin were significantly downregulated in females exposed to either LET or TAM, while they were significantly upregulated in TAM-exposed males and did not exhibit any change in LET-treated males. The expression of genes involved in steroidogenesis was also modulated by these two anti-estrogens in a way that corresponded with their anticipated mode of action. Overall, the data not only provide mechanistic information of anti-estrogenic chemicals but also demonstrate the potential of investigation of gene expression in the HPG(L) axis of model fish for diagnostic and predictive assessments of the risks associated with chemical exposure.