title: Triorganotin compounds--ligands for "rexinoid" inducible transcription factors: biological effects.
abstract: We review trialkyltin and triaryltin compounds, representing a class of organometallic compounds that function as nuclear retinoid X receptors (RXR) agonists due to their capability to bind to the ligand-binding domain of RXR subtypes and function as transcriptional activators. RXRs act predominantly as heterodimers with other nuclear receptors as permissive heterodimers with peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptor, pregnane X receptor and constitutive androstan receptor or as non-permissive heterodimer with vitamin D receptor, and as conditional heterodimers with retinoid receptors, and thyroid hormone receptors. RXR - "partner" receptor heterodimers are considered to be ligand-activated, DNA-binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. Tributyltin at even pico- or nanomolar concentrations may cause the superimposition of male genitalia on female in several aquatic organisms, since they are DNA-targeted, mitotic, and their actions are occurring through target gene(s)-mediated pathways. They may cause molecular interactions with reproductive system in mammals, and as potent environmental obesogens, they promote adipocyte differentiation. Organotin compounds become known also for their immunotoxicity, neurotoxicity, for their effects on reproduction and/or development. We also review effects of organotins with respect to levels and activities of hepatic P450s and aromatase activity.
authors: Laboratory of Molecular Endocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovak Republic. Electronic address: julius.brtko@savba.sk.
authors: J
authors: J
authors: Brtko
authors: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 11, 783 71 Olomouc, Czech Republic.
authors: Z
authors: Z
authors: Dvorak
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D009947:Organotin Compounds / Q000633:toxicity*; D047488:Retinoid X Receptors / Q000819:agonists; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004785:Environmental Pollutants; D009947:Organotin Compounds; D047488:Retinoid X Receptors; D014157:Transcription Factors
keywords: Antiproliferative effects; Cytochrom P-450; Environmental obesogen; Ligand inducible transcription factor; Metabolism; Nuclear receptor; Organotin compounds; Retinoid X receptor; Toxicity