Human and fish differences in steroid receptors activation: A review

Steroid receptors (SRs) are transcription factors activated by steroid hormones (SHs) that belong to the nuclear receptors (NRs) superfamily. Several studies have shown that SRs are targets of endocrine disrupting chemicals (EDCs), widespread substances in the environment capable of interfering with the endogenous hormonal pathways and causing adverse health effects in living organisms and/or their progeny. Cell lines with SRs reporter gene are currently used for in vitro screening of large quantities of chemicals with suspected endocrine-disrupting activities. However, most of these cell lines express human SRs and therefore the toxicological data obtained are also extrapolated to non-mammalian species. In parallel, in vivo tests have recently been developed on fish species whose data are also extrapolated to mammalian species. As some species-specific differences in SRs activation by natural and synthetic chemicals have been recently reported, the aim of this review is to summarize those between human and fish SRs, as representatives of mammalian and non-mammalian toxicology, respectively. Overall, this literature study aims to improve inter-species extrapolation of toxicological data on EDCs and to understand which reporter gene cell lines expressing human SRs are relevant for the assessment of effects in fish and whether in vivo tests on fish can be properly used in the assessment of adverse effects on human health.