Development of yeast reporter assays for the enhanced detection of environmental ligands of thyroid hormone receptors alpha and beta from Xenopus tropicalis

摘要

Thyroid hormones (THs) are involved in the regulation of metabolic homeostasis during the development and differentiation of vertebrates, particularly amphibian metamorphosis, which is entirely controlled by internal TH levels. Some artificial chemicals have been shown to exhibit TH-disrupting activities. In order to detect TH disruptors for amphibians, we herein developed a reporter assay using yeast strains expressing the thyroid hormone receptors (TRs) alpha and beta together with the transcriptional coactivator SRC-1, all of which were derived from the frog Xenopus tropicalis (XT). These yeast strains responded to endogenous THs (T-2, T-3, and T-4) in a dose-dependent manner. They detected the TR ligand activities of some artificial chemicals suspected to exhibit TH-disrupting activities, as well as TR ligand activity in river water collected downstream of sewage plant discharges, which may have originated from human excrement. Moreover, the responses of XT TR strains to these endogenous and artificial ligands were stronger than those of yeast strains for human TR alpha and beta assays, which had previously been established in our laboratory. These results indicate that the yeast reporter assay system for XT TRa and 3 is valuable for assessing TR ligand activities in environmental samples that may be particularly potent in amphibians. (C) 2016 Published by Elsevier Ltd.