Thyroid Hormone Deiodination in Birds

Abstract

Because the avian thyroid gland secretes almost exclusively thyroxine (T4), the availability of receptor-active 3,3',5-triiodothyronine (T3) has to be regulated in the extrathyroidal tissues, essentially by deiodination. Like mammals and most other vertebrates, birds possess three types of iodothyronine deiodinases (D1, D2, and D3) that closely resemble their mammalian counterparts, as shown by biochemical characterization studies in several avian species and by cDNA cloning of the three enzymes in chicken. The tissue distribution of these deiodinases has been studied in detail in chicken at the level of activity and mRNA expression. More recently specific antibodies were used to study cellular localization at the protein level. The abundance and distribution of the different deiodinases shows substantial variation during embryonic development and postnatal life. Deiodination in birds is subject to regulation by hormones from several endocrine axes, including thyroid hormones, growth hormone and glucocorticoids. In addition, deiodination is also influenced by external parameters, such as nutrition, temperature, light and also a number of environmental pollutants. The balance between the outer and inner ring deiodination resulting from the impact of all these factors ultimately controls T3 availability.

Effects of energy restriction on thyroid hormone metabolism in chickens

“…As a consequence of the decreased 5'D activity, less T 4 is converted to T 3 , which leads to an increase in the circulating concentration of T 4 (Darras et al, 2006). We also found increased T 4 concentrations in the restricted groups as compared to controls.…”

“…Decuypere et al (2005) and Kühn et al (2005) found that TRH is not thyrotropic (does not increase plasma concentration of T 4 ), but somatotropic [increases growth hormone (GH) plasma concentration] in adult chickens. TRH administration is followed by increased circulating concentration of GH, and GH decreases 5D (Darras et al, 2006), while it probably increases 5'D (Geris et al, 1998;Kühn et al, 2005). In this way, serum T 3 concentrations are not only decreased due to the reduced T 4 -to-T 3 conversion but also by the increased T 3 -to-T 2 degradation.…”

“…All these enzymes have been cloned and characterised: all contain selenium in the active site and remove single iodine atoms from the hormone molecules. D1 and D2 remove iodine from the outer ring (5' deiodination, 5'D) producing T 3 from T 4 , therefore 5'D is called the activating pathway (Bianco et al, 2002;Darras et al, 2006). D3 and in certain cases D1 remove iodine from the inner ring (5 deiodination, 5D) degrading T 3 or converting T 4 into r-T 3 ; therefore, 5D is called the inactivating pathway.…”

Iodothyronine deiodinases: a functional and evolutionary perspective

“…This differential response to PTU between mammalian D1 and the amphibian and teleostean orthologs probably reflects a difference in the function of the enzyme in these species. In mammals and chicken, D1 is usually highly expressed in the liver, which plays an important role in regulating plasma T 3 levels (reviewed in Darras et al (2006) and Gereben et al (2008)). By contrast, D1 function in teleostean and amphibian T 3 plasma regulation is less clear (Finnson et al 1999.…”

Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

“…Therefore, these are called hormoneexporting organs (116,117,119) . D2 is also expressed in the liver in birds but not in mammals (102) . Peripheral tissues can adjust the ratio of active and inactive thyroid hormones, according to their actual energy needs and energy supply through their deiodinase activity.…”