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Thyroid hormone transport evolved with albumin, then transthyretin, and finally thyroxine-binding globulin. These proteins are crucial for development and homeothermy in vertebrates.

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Area of Science:

  • Evolutionary biology
  • Endocrinology
  • Genetics

Background:

  • Thyroid hormones are essential for vertebrate development and metabolism.
  • The extracellular distribution network of thyroid hormones involves specific binding proteins.
  • Understanding the evolutionary origin of this network provides insights into vertebrate adaptation.

Purpose of the Study:

  • To investigate the evolutionary development of the thyroid hormone distribution network.
  • To correlate the appearance of transthyretin and thyroxine-binding globulin with developmental stages and metabolic changes.
  • To identify the role of liver-enriched transcription factors in gene expression.

Main Methods:

  • Comparative gene expression analysis of transthyretin and thyroxine-binding globulin across vertebrate species.
  • Examination of promoter regions for transcription factor binding sites (e.g., HNF-3beta/Foxa2).
  • Correlation of protein appearance with developmental transitions and homeothermy acquisition.

Main Results:

  • Albumin is the oldest component, present in all investigated vertebrates.
  • Transthyretin emerged later in vertebrate evolution, with liver expression linked to transcription factor binding sites.
  • Thyroxine-binding globulin appeared in marsupials/rodents postnatally and in most eutherians perinatally to adulthood.
  • The inclusion of these proteins correlates with developmental remodeling and increased metabolism for homeothermy.

Conclusions:

  • The thyroid hormone distribution network evolved sequentially, with albumin, transthyretin, and thyroxine-binding globulin added over time.
  • The evolution of transthyretin and thyroxine-binding globulin is linked to increased thyroid hormone demands during development and the acquisition of homeothermy.
  • Gene regulation by transcription factors plays a key role in the expression of transthyretin.