title: Trialkyltin Rexinoid-X Receptor Agonists Selectively Potentiate Thyroid Hormone Induced Programs of Xenopus laevis Metamorphosis.
abstract: The trialkyltins tributyltin (TBT) and triphenyltin (TPT) can function as rexinoid-X receptor (RXR) agonists. We recently showed that RXR agonists can alter thyroid hormone (TH) signaling in a mammalian pituitary TH-responsive reporter cell line, GH3.TRE-Luc. The prevalence of TBT and TPT in the environment prompted us to test whether they could also affect TH signaling. Both trialkyltins induced the integrated luciferase reporter alone and potentiated TH activation at low doses. Trimethyltin, which is not an RXR agonist, did not. We turned to a simple, robust, and specific in vivo model system of TH action: metamorphosis of Xenopus laevis, the African clawed frog. Using a precocious metamorphosis assay, we found that 1nM TBT and TPT, but not trimethyltin, greatly potentiated the effect of TH treatment on resorption phenotypes of the tail, which is lost at metamorphosis, and in the head, which undergoes extensive remodeling including gill loss. Consistent with these responses, TH-induced caspase-3 activation in the tail was enhanced by cotreatment with TBT. Induction of a transgenic reporter gene and endogenous collagenase 3 (mmp13) and fibroblast-activating protein-α (fap) genes were not induced by TBT alone, but TH induction was significantly potentiated by TBT. However, induction of other TH receptor target genes such as TRβ and deiodinase 3 by TH were not affected by TBT cotreatment. These data indicate that trialkyltins that can function as RXR agonists can selectively potentiate gene expression and resultant morphological programs directed by TH signaling in vivo.
authors.affiliation: Department of Neurobiology, Physiology and Behavior (B.J.M., J.D.F.), University of California Davis, Davis, California 95695; and Marine Animal Ecology Group (A.J.M.), Wageningen University, 6700 AH Wageningen, The Netherlands.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Mengeling
authors.affiliation: Department of Neurobiology, Physiology and Behavior (B.J.M., J.D.F.), University of California Davis, Davis, California 95695; and Marine Animal Ecology Group (A.J.M.), Wageningen University, 6700 AH Wageningen, The Netherlands.
authors.forename: Albertinka J
authors.initials: AJ
authors.lastname: Murk
authors.affiliation: Department of Neurobiology, Physiology and Behavior (B.J.M., J.D.F.), University of California Davis, Davis, California 95695; and Marine Animal Ecology Group (A.J.M.), Wageningen University, 6700 AH Wageningen, The Netherlands.
authors.forename: J David
authors.initials: JD
authors.lastname: Furlow
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000187:drug effects*; D009947:Organotin Compounds / Q000494:pharmacology; D047488:Retinoid X Receptors / Q000819:agonists*; D000637:Transaminases / Q000494:pharmacology*; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014298:Trimethyltin Compounds / Q000494:pharmacology; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D009947:Organotin Compounds; D047488:Retinoid X Receptors; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; C011559:tributyltin; C030665:triphenyltin; D000637:Transaminases; C023165:thyroid hormone aminotransferase; D053148:Caspase 3; D053509:Matrix Metalloproteinase 13