Thyroid hormone and development: the importance of transporters and deiodinases

Thyroid hormone, which is the common name for the prohormone T4 (3,5,3’,5’-tetraiodothyronine; thyroxine) and the bioactive hormone T3 (3,5,3’-triiodothyronine), is indispensable for normal development and metabolism of all tissues. Its effects on metabolism are clearly illustrated by the clinical manifestations in primary thyroid diseases. In hypothyroidism, symptoms such as cold intolerance, constipation, weight gain and bradycardia result from a generalized slowing of metabolic processes. In contrast, heat intolerance, weight loss and increased heart rate which are observed in patients with hyperthyroidism are explained by an increased metabolism. The prerequisite of thyroid hormone for normal development is clearly exemplified by patients with cretinism. Insufficient supply of iodine, which is a principal component of thyroid hormone, during critical periods of development may result in severe and permanent growth impairments, deafness, motor and mental retardation. Clinical effects of an altered thyroid state arise from changes in thyroid hormone physiology at the cellular level. Thyroid hormone homeostasis requires adequate function of transporter proteins, deiodinating enzymes and nuclear receptors at the level of thyroid hormone target tissues