PMID- 30448381 OWN - NLM STAT- MEDLINE DCOM- 20190219 LR - 20200309 IS - 1095-6840 (Electronic) IS - 0016-6480 (Print) IS - 0016-6480 (Linking) VI - 272 DP - 2019 Feb 1 TI - Effects of thyroid hormone disruption on the ontogenetic expression of thyroid hormone signaling genes in developing zebrafish (Danio rerio). PG - 20-32 LID - S0016-6480(18)30305-8 [pii] LID - 10.1016/j.ygcen.2018.11.007 [doi] AB - Thyroid hormones (THs) regulate neurodevelopment, thus TH disruption is widely posited as a mechanism of developmental neurotoxicity for diverse environmental chemicals. Zebrafish have been proposed as an alternative model for studying the role of TH in developmental neurotoxicity. To realize this goal, it is critical to characterize the normal ontogenetic expression profile of TH signaling molecules in the developing zebrafish and determine the sensitivity of these molecules to perturbations in TH levels. To address these gaps in the existing database, we characterized the transcriptional profiles of TH transporters, deiodinases (DIOs), receptors (TRs), nuclear coactivators (NCOAs), nuclear corepressors (NCORs), and retinoid X receptors (RXRs) in parallel with measurements of endogenous TH concentrations and tshbeta mRNA expression throughout the first five days of zebrafish development. Transcripts encoding these TH signaling components were identified and observed to be upregulated around 48-72 h post fertilization (hpf) concurrent with the onset of larval production of T4. Exposure to exogenous T4 and T3 upregulated mct8, dio3-b, tralpha-a, trbeta, and mbp-a levels, and downregulated expression of oatp1c1. Morpholino knockdown of TH transporter mct8 and treatment with 6-propyl-2-thiouracil (PTU) was used to reduce cellular uptake and production of TH, an effect that was associated with downregulation of dio3-b at 120 hpf. Collectively, these data confirm that larval zebrafish express orthologs of TH signaling molecules important in mammalian development and suggest that there may be species differences with respect to impacts of TH disruption on gene transcription. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Walter, Kyla M AU - Walter KM AD - Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, United States. Electronic address: kwalter@ucdavis.edu. FAU - Miller, Galen W AU - Miller GW AD - Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, United States. Electronic address: gwmiller@ucdavis.edu. FAU - Chen, Xiaopeng AU - Chen X AD - Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, United States. Electronic address: chenxiaopengemail@gmail.com. FAU - Yaghoobi, Bianca AU - Yaghoobi B AD - Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, United States. Electronic address: byaghoobi@ucdavis.edu. FAU - Puschner, Birgit AU - Puschner B AD - Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, United States. Electronic address: bpuschner@ucdavis.edu. FAU - Lein, Pamela J AU - Lein PJ AD - Department of Molecular Biosciences, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, United States. Electronic address: pjlein@ucdavis.edu. LA - eng GR - T32 ES007059/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20181115 PL - United States TA - Gen Comp Endocrinol JT - General and comparative endocrinology JID - 0370735 RN - 0 (Thyroid Hormones) SB - IM MH - Animals MH - Gene Expression Regulation, Developmental/*genetics MH - Thyroid Gland/*metabolism MH - Thyroid Hormones/*metabolism MH - Transcriptome/*genetics MH - Zebrafish/*genetics PMC - PMC6331280 MID - NIHMS1515234 OTO - NOTNLM OT - Endocrine disruption OT - Thyroid hormone OT - Transcriptomics OT - Zebrafish EDAT- 2018/11/19 06:00 MHDA- 2019/03/21 06:00 PMCR- 2020/02/01 CRDT- 2018/11/19 06:00 PHST- 2018/05/28 00:00 [received] PHST- 2018/11/12 00:00 [revised] PHST- 2018/11/14 00:00 [accepted] PHST- 2018/11/19 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] PHST- 2018/11/19 06:00 [entrez] PHST- 2020/02/01 00:00 [pmc-release] AID - S0016-6480(18)30305-8 [pii] AID - 10.1016/j.ygcen.2018.11.007 [doi] PST - ppublish SO - Gen Comp Endocrinol. 2019 Feb 1;272:20-32. doi: 10.1016/j.ygcen.2018.11.007. Epub 2018 Nov 15.