Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

Abstract

It is widely accepted that type II iodothyronine deiodinase (D2) is mostly present in the brain, where it maintains the homeostasis of thyroid hormone (TH) levels. Although intensive studies have been performed on activity and mRNA levels of the deiodinases, very little is known about their expression at the protein level due to the lack of specific antisera. The current study reports the production of a specific D2 polyclonal antiserum and its use in the comparison of D2 protein distribution with that of type I (D1) and type III (D3) deiodinase protein in the choroid plexus at the blood-brain barrier level. Immunocytochemistry showed very high D2 protein expression in the choroid plexus, especially in the epithelial cells, whereas the D1 and D3 proteins were absent. Furthermore, dexamethasone treatment led to an up-regulation of the D2 protein in the choroid plexus. The expression of D2 protein in the choroid plexus led to a novel insight into the working mechanism of the uptake and transport of thyroid hormones along the blood-brain barrier in birds. It is hypothesized that D2 allows the prohormone thyroxine (T 4 ) to be converted into the active 3,5,3 -triiodothyronine (T 3 ). Within the choroidal epithelial cells. T 3 is subsequently bound to its carrier protein, transthyretin (TTR), to allow transport through the cerebrospinal fluid. Neurons can thus not only be provided with a sufficient T 3 level via the aid of the astrocytes, as was hypothesized previously based on in situ hybridization data, but also by means of T 4 deiodination by D2, directly at the blood-brain barrier level.

Thyroid Hormone Deiodination in Birds

“…New, however, was the detection of high D2 protein levels in the cuboidal epithelial cells of the embryonic choroid plexus (Fig 2), while both D1 and D3 were absent from this structure (29). This is different from results obtained so far in adult rat, where no D2 has been found in the choroid plexus.…”

“…Now that these are available for chicken D1 (28), D2 (29), and D3 (30), the cellular localization of these enzymes is progressing rapidly. Both D1 and D3 protein are found in hepatocytes, with the highest levels in the layers immediately surrounding the blood vessels (31).…”

“…The presence of D2 in the avian choroid plexus allows for an additional mechanism of T 3 supply to the neurons via direct deiodination of T 4 in the ependymal cells. Given the fact that avian transthyretin, in contrast to mammalian, shows a higher affinity for T 3 than T 4 (34), T 3 can be transported directly from the choroidal epithelium to the neurons (29). Apart from being species specific, there is also the possibility that the expression of D2 in the embryonic chicken choroid plexus is temporary and thus a transient development related event.…”

Synthesis of Thyroid Hormone Binding Proteins Transthyretin and Albumin by Human Trophoblast

“…Type 2 deiodinase has been reported in chicken choroid plexus in which it generates T 3 from T 4 . TTR then, it is postulated, carries T 3 into cerebrospinal fluid (21). TTR has also been found in low levels in heart, stomach, skeletal muscle, and spleen of the rat (22).…”

Role of type 1 and 2 deiodinases in thyroid metabolism (review)

“…Негативные последствия дефицита Д2 при развитии ЦНС могут быть ослаблены другими источниками Т3, такими как цереброспинальная жидкость и сыворотка кро-ви [26]. Присутствие Д2 в хороидном сплетении эм-брионов птиц и человека указывает на дополнитель-ную возможность поступления Т3 в нейроны [27].…”