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Temporal Pole Responds to Subtle Changes in Local Thyroid Hormone Signaling.

Cícera P Marcelino1,2, Elizabeth A McAninch3, Gustavo W Fernandes4

  • 1Department of Health and Biological Sciences - CCBS, Mackenzie Presbyterian University, Sao Paulo, Sao Paulo, Brazil.

Journal of the Endocrine Society
|October 30, 2020
PubMed
Summary

Thyroid hormone (TH) signaling in the human temporal pole was assessed using gene expression. TH signaling index (T3S+) correlated with TH transporters, TR beta, and coregulators, revealing insights into brain TH regulation.

Keywords:
braingene expression profilehypothyroidismthyroid hormones

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genomics

Background:

  • Thyroid hormones (TH) are crucial for brain development and function.
  • Understanding TH signaling in the adult human brain is essential for neurological health.
  • Previous studies have primarily focused on developmental stages or animal models.

Purpose of the Study:

  • To investigate thyroid hormone (TH) signaling in the adult human temporal pole (Brodmann area 38).
  • To identify genes and pathways regulated by local TH signaling in the human brain.
  • To establish a gene expression-based index for TH signaling in human brain tissue.

Main Methods:

  • Analysis of published microarray data from 19 deceased human brain donors.
  • Development of a TH signaling index (T3S+) based on 19 mouse-validated TH-responsive genes.
  • Factor analysis and transcriptome-wide correlation to identify gene sets associated with T3S+.
  • Utilized Gene Ontology (GO) and Molecular Signatures Data Base (MSigDB) for pathway enrichment analysis.

Main Results:

  • The T3S+ index showed variation across individuals and correlated with TH transporters (MCT8, LAT2) and specific TH receptor (TR) beta components.
  • Unexpectedly, no correlation was observed with DIO2, DIO3, SRC1, or TR alpha.
  • Systematic transcriptome analysis identified gene sets enriched for synaptic transmission and metabolic processes, correlating with T3S+.
  • A significant overlap of 769 genes (set #5) demonstrated strong association with T3S+ and shared functional signatures.

Conclusions:

  • Gene expression in the human temporal pole can be effectively assessed using the T3S+ index.
  • Local TH signaling in the human brain exhibits subtle variations that influence gene expression.
  • This study provides a framework for studying TH signaling in the adult human brain at the molecular level.