5.08 – Thyroid Hormones and Brain Development

Thyroid hormones (THs) are essential for brain maturation and function. Conditions associated with impaired action of THs in the brain during development include iodine deficiency, maternal and fetal hypothyroidism, maternal hypothyroxinemia, prematurity, and mutations of TH transporters and nuclear receptors. All these conditions may lead to various degrees of mental retardation and neurological impairment. This chapter is a review of the pathophysiology of TH action in the brain. First, an analysis is made of the factors that control the tissue concentration and action of the active hormone triiodothyronine (T3), such as thyroidal secretion, tissue expression of deiodinases, cellular transporters, and nuclear receptors. This is followed by a survey of the genes regulated by THs in brain and, finally, by a description of clinical situations caused by defective TH signaling in an attempt to explain these syndromes with our present knowledge of TH physiology and action at the molecular level.