I. Introduction FOR YEARS thyroid hormones have been known to be important for normal neonatal brain development, and numerous reviews have covered this topic in depth. It now also appears that fetal thyroid hormones play an essential role in fetal braindevelopment. In addition, as some placental transport of thyroid hormones has been shown to occur, it is possible that maternal thyroid hormones might influence fetal brain development.
II. The Value of the Use of Animal Models in the Comprehension of the Role of Thyroid Hormones in Neurological Development Animal models have been used to study the influence of thyroid hormones on neurological]evelopment. Rats and mice have been the primary animals studied; however, a significant amount of data have come from studies on sheep and nonhuman primates. While the merit of application of animal data to human problems is frequently questioned, valuable information can be obtained when the animal data are properly interpreted. Furthermore, most of the information obtained from animal experimentswould be unavailable from humans.
Copyright © 2007 by The Endocrine Society
Articles citing this article
Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the second trimester, a period of high sensitivity of the brain to thyroid hormones. In the rat, theequivalent period is the last quarter of pregnancy. However, little is known about thyroid hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated genes have been identified during the postnatal period. To identify potential targets of thyroid hormone in the fetal brain, we induced maternal and fetal hypothyroidism by maternal thyroidectomy followed by antithyroid drug(2-mercapto-1-methylimidazole) treatment. Microarray analysis identified differentially expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after conception. Gene function analysis revealed genes involved in the biogenesis of the cytoskeleton, neuronal migration and growth, and branching of neurites. Twenty percent of the differentially expressed genes were related to each othercentered on the Ca2+ and calmodulin-activated kinase (Camk4) pathway. Camk4 was regulated directly by T3 in primary cultured neurons from fetal cortex, and the Camk4 protein was also induced by thyroid hormone. No differentially expressed genes were recovered when euthyroid fetuses from hypothyroid mothers were compared with fetuses from normal mothers. Although the results do not rule out a specificcontribution from the mother, especially at earlier stages of pregnancy, they indicate that the main regulators of thyroid hormone-dependent, fetal brain gene expression near term are the fetal thyroid hormones.
El papel de las hormonas tiroideas en Neurológicos prenatal y neonatal para el Desarrollo-
I. Introducción de las hormonas tiroideas AÑOS han sido conocidos por serimportantes para el desarrollo normal del cerebro neonatal, y numerosas críticas han cubierto este tema en profundidad. Ahora también parece que las hormonas de tiroides fetal juegan un papel esencial en el desarrollo del cerebro fetal. Además, como parte del transporte de la placenta de las hormonas tiroideas se ha demostrado que se producen, es posible que las hormonas tiroideas maternas podríaninfluir en el desarrollo del cerebro fetal.
II. El valor de la utilización de modelos animales en la comprensión del papel de las hormonas tiroideas en los modelos de desarrollo neurológico en animales han sido utilizados para estudiar la influencia de las hormonas tiroideas sobre neurológico]esarrollo. Las ratas y ratones han sido los animales primaria estudiada, sin embargo,una cantidad...