RXR Ligands Modulate Thyroid Hormone Signaling Competence in Young Xenopus laevis Tadpoles

Endocrinology
Brenda J MengelingJ D Furlow

Abstract

Appropriate thyroid hormone (TH) signaling through thyroid hormone receptors (TRs) is essential for vertebrate development. Amphibian metamorphosis is initiated and sustained through the action of TH on TRs, which are conserved across vertebrates. TRs heterodimerize with retinoid X receptors (RXRs) on thyroid hormone response elements (TREs) in the genome; however, in most cell line and adult animal studies, RXR ligands do not affect expression of TR target genes. We used a quantitative, precocious metamorphosis assay to interrogate the effects of the RXR agonist bexarotene (Bex) and the RXR antagonist UVI 3003 (UVI) on T3-induced resorption phenotypes in Xenopus laevis tadpoles 1 week postfertilization. Bex potentiated gill and tail resorption, and UVI abrogated T3 action. These results held in transgenic tadpoles bearing a TRE-driven luciferase reporter. Therefore, we used poly-A-primed RNA sequencing transcriptomic analysis to determine their effects on T3-induced gene expression. We also assayed the environmental pollutant tributyltin (TBT), which is an RXR agonist. We found that the proteases that carry out resorption were potentiated by Bex and TBT but were not significantly inhibited by UVI. However, several transcriptio...Continue Reading

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Citations

Aug 23, 2018·Development, Growth & Differentiation·Sho MoriokaIchiro Tazawa
Aug 15, 2018·International Journal of Molecular Sciences·Masaki Watanabe, Hiroki Kakuta
May 31, 2020·Psychopharmacology·Eric Murillo-RodríguezPablo Torterolo
Mar 10, 2020·Molecular and Cellular Endocrinology·Stephan CouderqJean-Baptiste Fini
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Jan TaubenheimSebastian Fraune

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