Disruption of Feedback Regulation of Thyroid Hormone Synthesis/Secretion and Brain Development

Abstract

The hypothalamic–pituitary–thyroid axis plays a central role in the regulation of thyroid hormone homeostasis. The hypothalamus arises from diencephalon and the hormone-producing nuclei have neuronal origin. The anterior and intermediate lobes of the pituitary gland originate from the oral ectoderm, whereas the posterior lobe is derived from the neural ectoderm. Hypothalamic TRH stimulates pituitary TSH, and TSH stimulates the production of thyroid hormone. Conversely, thyroid hormone suppresses TRH and TSH. Impairment of TRH signaling or TSH signaling results in central hypothyroidism. Central hypothyroidism is much less common compared to primary hypothyroidism. Congenital central hypothyroidism is induced by several disorders including tumors, developmental defects, and gene mutations. Patients with congenital central hypothyroidism can suffer from mental retardation, poor verbal skills, attention deficits, and motor weakness, similarly to those with congenital primary hypothyroidism. In addition to the effect of hypothyroidism, the defects in TRH signaling or TSH signaling might disturb the development of the brain.