Regulators of thyroid hormone availability and action in embryonic chicken brain development

Abstract

Thyroid hormones (THs) are crucial elements in vertebrate brain development. They exert their action mainly through binding of 3,5,3'-triiodothyronine (T3) to nuclear receptors that directly influence the expression of TH-regulated genes. Intracellular TH action is therefore dependent on both the availability of T3 and its receptors. TH uptake in cells is regulated by specific TH transporters and local activation and inactivation is regulated by deiodinases. This review provides an overview of the general expression pattern of TH transporters, deiodinases and receptors during embryonic chicken brain development and compares it to the situation in mammals. It is clear that THs and their regulators are present in the embryonic brain from the early stages of development, long before the onset of embryonic thyroid gland functioning. The mechanism of TH uptake across the brain barriers during development is only partly understood. At the developing blood-brain-barrier expression of the TH-activating type 2 deiodinase is closely associated with the blood vessels, but contrary to the situation in (adult) mammals no expression of MCT8 or OATP1C1 TH transporters is found at that level in the developing chicken. At the blood-cerebrospinal fluid-barrier co-expression of the TH-inactivating type 3 deiodinase and MCT8 and OATP1C1 is found in birds and mammals. These comparative data show overlapping patterns, pointing to general mechanisms, but also indicate specific interspecies differences that may help to understand species-specific responses to regulator gene knockout/mutation.

Keywords: AHDS; Allan-Herndon-Dudley syndrome; BBB; BCSFB; Brain barriers; Brain development; CSF; Chicken; D2; D3; Deiodinases; E#; IRD/ORD; ISH; L-type amino acid transporter; LAT; MCT; Mammals; OATP; TH; TH receptors; TH transporters; TR; TTR; Thyroid hormones; blood–brain-barrier; blood–cerebrospinal fluid-barrier; cerebrospinal fluid; embryo of # days old; in situ hybridisation; inner/outer ring deiodination; monocarboxylate transporter; organic anion transporting polypeptide; rT(3); reverse T(3); thyroid hormone; thyroid hormone receptor; transthyretin; type 2 deiodinase; type 3 deiodinase.