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An Ex vivo Culture System to Study Thyroid Development
08:33

An Ex vivo Culture System to Study Thyroid Development

Published on: June 6, 2014

Short-term effects of thyroid hormones during development: Focus on signal transduction

Sergio Scapin1, Silvia Leoni, Silvana Spagnuolo

  • 1Department of Cellular and Developmental Biology, Sapienza University, 00185 Rome, Italy.

Steroids
|November 11, 2009
PubMed

Insights

Thyroid hormones exert rapid, nongenomic effects through membrane receptors like alphaVbeta3 integrin, influencing cell transport systems and mitogenesis independently of protein synthesis. These actions complement traditional nuclear receptor pathways for maintaining cellular function.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Signaling

Background:

  • Thyroid hormones (THs) traditionally act via nuclear receptors to regulate gene expression.
  • Extranuclear or nongenomic effects of THs are rapid and independent of protein synthesis.
  • Emerging evidence highlights membrane receptors and TH metabolites in mediating these nongenomic actions.

Purpose of the Study:

  • To review the mechanisms and targets of thyroid hormone nongenomic effects.
  • To highlight the role of the alphaVbeta3 integrin as a key membrane receptor for THs.
  • To discuss the implications of nongenomic TH actions on cellular transport and mitogenesis.

Main Methods:

  • Literature review of recent findings on thyroid hormone nongenomic signaling.
  • Identification of key receptors (e.g., alphaVbeta3 integrin, cytoplasmic TRalpha/beta, GPCRs) and signaling pathways (PKC, Src, MAPK).
  • Analysis of TH modulation of Na(+)-dependent transport systems (Na(+)/K(+)-ATPase, Na(+)/H(+) exchanger, System A).

Main Results:

  • The alphaVbeta3 integrin is a significant cell membrane receptor for THs, mediating diverse nongenomic effects.
  • THs activate multiple intracellular signaling cascades (PKC, Src, MAPK) via membrane receptors.
  • Nongenomic TH signaling modulates critical ion and amino acid transporters, impacting cell proliferation, particularly in embryonic cells.

Conclusions:

  • Thyroid hormones engage in rapid, nongenomic signaling through various membrane and cytoplasmic receptors, including alphaVbeta3 integrin.
  • These nongenomic pathways modulate essential cellular transport systems, contributing to cellular functions like mitogenesis.
  • Nongenomic actions of THs complement nuclear pathways, reinforcing their fundamental role in maintaining cellular homeostasis.

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