Hormonas Tiroideas y Cerebro. Notas Sobre La Relación Bocio y ...

The DNA-bound, ligand-free TR, or aporeceptor interacts with corepressors and inhibit target gene
transcription. Hormone binding induces a conformational change of the receptor which facilitates
corepressor dissociation, binding of coactivators and stimulation of transcription.
In the human, T 3 receptors are present in brain after 8–10 weeks of gestation. In subsequent
weeks, the receptor concentration greatly increases in brain and other tissues, supporting the view of
an important role of thyroid hormones on developmental processes taking place during the second
trimester (8).
In the rat brain, the T 3 receptor is already present at embryonic day 14 (E14), and messenger
RNA for the receptor is present by E11.5 in the neural tube and by E12.5 in certain areas of the
diencephalon and ventral rhombencephalon (9). Despite this, most actions of thyroid hormones
during rat brain development occur after birth, and many genes are thyroid hormone-dependent during
the first two postnatal weeks. Nevertheless, actions of thyroid hormones on cell migration in the
cerebral cortex have been found before onset of fetal thyroid gland function, stressing the importance
of maternally derived hormones (4).
Both thyroid hormone receptor genes—THRA and THRB—are expressed in brain, with
partially unique and partially overlapping patterns, but the product of the THRA gene, TR1, accounts
for 70-80% of al T3 receptor (8). Most effects of thyroid hormone in brain are therefore likely to be
mediated through this receptor subtype. However, TR1 deletion does not cause the same
impairments of brain development as hypothyroidism. We have shown that the difference between
hypothyroidism and receptor deletion is that in the former, the activity of the unliganded receptor may
interfere with developmental processes (10).
References.
1. Delong GR, Stanbury JB, Fierro-Benítez R 1985 Neurological signs in congenital iodine-deficiency disorder
(endemic cretinism). Develop Med Child Neurol, 27:317-324.
2. Guadaño-Ferraz A, Obregon MJ, St Germain DL, Bernal J 1997 The type 2 iodothyronine deiodinase is
expressed primarily in glial cells in the neonatal rat brain. Proc Natl Acad Sci USA 94:10391-10396.
3. Tu HM, Legradi G, Bartha T, Salvatore D, Lechan RM, Larsen PR 1999 Regional expression of the type 3
iodothyronine deiodinase messenger ribonucleic acid in the rat central nervous system and its regulation by
thyroid hormone. Endocrinology 140:784-790.
4. Morreale de Escobar G, Obregon MJ, Escobar del Rey F 2004 Role of thyroid hormone during early brain
development. Eur J Endocrinol 151: Suppl 3, U25-37.
5. Bernal J, Guadaño-Ferraz A, Morte B 2003 Perspectives in the study of thyroid hormone action on brain
development and function. Thyroid 13: 1005-1012.
6. Anderson GW, Schoonover CM, Jones SA 2003 Control of thyroid hormone action in the developing rat brain.
Thyroid 13:1039-1056.
7. O'Shea PJ, Williams GR 2002 Insight into the physiological actions of thyroid hormone receptors from
genetically modified mice. J Endocrinol 175: 553-570.
8. Bernal J 2007 Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol
Metab, 3:249-259.
9. Bradley DJ, Towle HC, Young WS, 3rd 1992 Spatial and temporal expression of alpha- and beta-thyroid
hormone receptor mRNAs, including the beta 2-subtype, in the developing mammalian nervous system. J
Neurosci 12:2288-2302.
10. Morte B, Manzano J, Scanlan T, Vennstrom B, Bernal J 2002 Deletion of the thyroid hormone receptor alpha
1 prevents the structural alterations of the cerebellum induced by hypothyroidism. Proc Natl Acad Sci U S A
99:3985-3989.
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