Evolutionary changes to transthyretin: developmentally regulated and tissue-specific gene expression

A survey of the expression of the transthyretin and thyroxine-binding globulin genes in various species during development provides clues as to how the present thyroid hormone distribution network in extracellular compartments developed during vertebrate evolution. Albumin may be the 'oldest' component of the thyroid hormone distribution network as it is found in the plasma of all vertebrates investigated. Subsequent to albumin, transthyretin appeared as the second component in this network during the evolution of vertebrates. The strong expression of transthyretin genes in the liver coincides with the presence of recognition site(s) for liver-enriched transcription factors, such as HNF-3β (Foxa2), in the transthyretin promoter regions of vertebrates. Finally, the addition of thyroxine-binding globulin to this network occurred at postnatal stages in some marsupials and rodents and in perinatal to adult stages in most eutherians. All vertebrates have defined developmental stages when thyroid hormone-dependent transition from larval to juvenile forms occurs. The inclusion of transthyretin and thyroxine-binding globulin in the thyroid hormone distribution network may be correlated with the increased requirement of thyroid hormones for thyroid hormone-dependent tissue remodeling during these stages and/or increased metabolism in thyroid hormone-target tissues with the acquisition of homeothermy.