Thyroid hormone receptors developing brain

M.A. Haidar, S. Dube and P.K. Sarkar. Thyroid hormone receptors of developing chick brain are predominantly in the neurons. Biochem. Biophys. Res. Commun. 112 221-227 (1983). 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

Thyroid hormone is essential for normal development of the human brain (Calvo, 1990 Morreale de Escobar et al. 2000). Numerous factors are involved in controlling the levels of receptor-active thyroid hormone, and disruption of any of these at critical phases of human development can lead to severe and persistent cognitive and motor deficits (Haddow, 1999). 

Ph. De Nayer and B. Dozin. Thyroid hormones and brain development modulation of the binding activity of the T3 nuclear receptor by chromatin-associated factors. Molec. Physiol. 7 303-310 (1985). 

In primary cultures from developing rat or mouse cerebellum no such effects on proliferation of EGL cells has been demonstrated (Messer et al. 1984, 1985), although effects on the number of glial cells were found. However, it is not clear whether proliferation of EGL cells occurs at sufficient levels in these cultures to show effects even if they were present. Thus, this issue must await further clarification. Also there is some question as to whether all postnatal germinal zones respond to thyroid hormones in the same way (Seress, 1977, 1978). However, the presence of specific nuclear receptors for thyroid hormones during brain development, (see Chapter by DeNayer) is consistent with the possibility that effects of thyroid hormones on cell proliferation, where they do exist, could occur by direct interactions with the genome. 

Endogenous T3 contents in fetal cerebra and cerebella all increased with development within 20th-36th weeks and showed a significant correlation with MBC of nuclear T3 receptor. This, therefore, corresponded closely to the dependence of fetal brain development on thyroid hormones in pregnancy. 

In conclusion, we have obtained a whole set of data about the relation between the fetal brain development and T3 and its nuclear receptor. It has also been shown clearly that the dependence of tissue development on thyroid hormone was mediated chiefly through the regulation of nuclear T3 and its receptor levels rather than altering its receptor occupancy. 

Carrasco, E., Blum, M., Weickert, C. S., and Casper, D. (2003). Epidermal growth factor receptor expression is related to post-mitotic events in cerebellar development Regulation by thyroid hormone. Brain Res. Dev. Brain Res. 140, 1-13. 

In the adult brain, receptors have been identified, but the specific genes affected by thyroid hormones have not yet been located. However, in the developing brain of the fetus and neonate, the effects of... 

Bockmann J, Winter C, Wittkowski W, Kreutz MR, Bockers TM (1997) Cloning and expression of a brain-derived TSH receptor. Biochem Biophys Res Commun 238 173-1780 Castagiola A, Swillens S, Niccoli P, Dumont JE, Vassart G, Ludgate M (1992) Binding assay for thyrotropin receptor autoantibodies using the recombinant receptor protein. J Clin Endocrinol Metab 75 1540-1544 Cole ES, Lee K, Lauziere K et al. (1993) Recombinant human thyroid stimulating hormone development of a biotech-... 

---