PMID- 29762675
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20200225
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 159
IP  - 7
DP  - 2018 Jul 1
TI  - RXR Ligands Modulate Thyroid Hormone Signaling Competence in Young Xenopus laevis 
      Tadpoles.
PG  - 2576-2595
LID - 10.1210/en.2018-00172 [doi]
AB  - 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 transcription factors from 
      multiple families (sox4, fosl2, mxd1, mafb, nfib) were all inhibited by UVI and 
      potentiated by Bex and TBT. All required T3 for induction. Time course analysis 
      of gene expression showed that although the agonists could potentiate within 12 
      hours, the antagonist response lagged. These data indicate that the agonists and 
      antagonist are not necessarily functioning through the same mechanism and suggest 
      that RXR liganding may modulate TH competence in metamorphic signaling.
FAU - Mengeling, Brenda J
AU  - Mengeling BJ
AD  - Department of Neurobiology, Physiology and Behavior, College of Biological 
      Sciences, University of California, Davis, Davis, California.
FAU - Goodson, Michael L
AU  - Goodson ML
AD  - Department of Anatomy, Physiology and Cell Biology, College of Veterinary 
      Medicine, University of California, Davis, Davis, California.
FAU - Furlow, J David
AU  - Furlow JD
AD  - Department of Neurobiology, Physiology and Behavior, College of Biological 
      Sciences, University of California, Davis, Davis, California.
LA  - eng
GR  - R21 ES026271/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thyroid Hormones)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation, Developmental/genetics/physiology
MH  - Larva/genetics/*metabolism
MH  - Receptors, Thyroid Hormone/genetics/*metabolism
MH  - Retinoid X Receptors/genetics/*metabolism
MH  - Thyroid Hormones/genetics/*metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Xenopus laevis/genetics/*metabolism
PMC - PMC6692881
EDAT- 2018/05/16 06:00
MHDA- 2019/02/12 06:00
PMCR- 2019/05/11
CRDT- 2018/05/16 06:00
PHST- 2018/02/15 00:00 [received]
PHST- 2018/05/07 00:00 [accepted]
PHST- 2018/05/16 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2018/05/16 06:00 [entrez]
PHST- 2019/05/11 00:00 [pmc-release]
AID - 4994597 [pii]
AID - endo_201800172 [pii]
AID - 10.1210/en.2018-00172 [doi]
PST - ppublish
SO  - Endocrinology. 2018 Jul 1;159(7):2576-2595. doi: 10.1210/en.2018-00172.