Thyroid Hormone Distributor Proteins During Development in Vertebrates

Abstract

Thyroid hormones (THs) are ancient hormones that not only influence the growth, development and metabolism of vertebrates but also affect the metabolism of (at least some) bacteria. Synthesized in the thyroid gland (or follicular cells in fish not having a discrete thyroid gland), THs can act on target cells by genomic or non-genomic mechanisms. Either way, THs need to get from their site of synthesis to their target cells throughout the body. Despite being amphipathic in structure, THs are lipophilic and hence do not freely diffuse in the aqueous environments of blood or cerebrospinal fluid (in contrast to hydrophilic hormones). TH Distributor Proteins (THDPs) have evolved to enable the efficient distribution of THs in the blood and cerebrospinal fluid. In humans, the THDPs are albumin, transthyretin (TTR), and thyroxine-binding globulin (TBG). These three proteins have distinct patterns of regulation in both ontogeny and phylogeny. During development, an additional THDP with higher affinity than those in the adult, is present during the stage of peak TH concentrations in blood. Although TTR is the only THDP synthesized in the central nervous system (CNS), all THDPs from blood are present in the CSF (for each species). However, the ratio of albumin to TTR differs in the CSF compared to the blood. Humans lacking albumin or TBG have been reported and can be asymptomatic, however a human lacking TTR has not been documented. Conversely, there are many diseases either caused by TTR or that have altered levels of TTR in the blood or CSF associated with them. The first world-wide RNAi therapy has just been approved for TTR amyloidosis.

Advanced Maternal Age, Mode of Delivery, and Thyroid Hormone Levels in Chinese Newborns

“…Our study also found that newborns born via C-section delivery had higher cord serum FT3 than those born via vaginal delivery. This might be due to the decreased levels of thyroid hormone distributer proteins (THDPs) which include albumin, transthyretin (TTR), and thyroxine-binding globulin (TBG) (53). As albumin, TTR and TBG are negative acute phase plasma proteins, all of them will be down-regulated in situations of stress or surgery (53), resulting in increased FT3.…”

The Role of the Thyroid Axis in Fish

“…In mammals, there is clear evidence that increased TH production/release induces increases in metabolic rate ( 2 ), weight loss ( 3 ), and cardiac output ( 4 ), while decreased TH production/release leads to opposite effects. In all vertebrates, THs are key hormones that influence a number of physiological processes including growth, development/morphogenesis, and metabolism ( 5 ). However, in fish, the role of the thyroid is incompletely understood.…”

Liver at the nexus of rat postnatal HPA axis maturation and sexual dimorphism

“…Circulating TSH acts on the thyroid to produce predominantly T4, which is converted to its active form triiodothyronine (T3) in peripheral tissue, and the access of thyroid hormones to their target tissues is influenced by TBG. Other liverexpressed plasma proteins, transthyretin and albumin, also bind thyroid hormones in the human and rodent (15 and 10% of human plasma T4, respectively) but with much lower affinity than TBG (Rabah et al 2019) and they do not appear to be required for thyroid hormone homeostasis in humans (Woeber & Ingbar 1968).…”