Chapter 21 - Thyroid Hormones

Abstract

Thyroid hormone is a peptide-derived hormone that acts predominantly on nuclear hormone receptors, although it can also act through nongenomic pathways. Thyroid hormone action is regulated at several levels, activation of the prohormone, tissue-specific distribution of thyroid hormone receptor isoforms, and transcription coregulators. Some tissues, such as the brain, have specific thyroid hormone membrane transporters that regulate intracellular ligand availability. Iodine is required for thyroid hormone synthesis and is transported into the thyroid gland by the sodium iodide symporter, a member of the sodium-dependent solute transporter family. Thyroid hormone has important direct actions in development and is essential for normal growth, brain, and sensory development. In the adult, thyroid hormone is important for metabolic regulation and has actions on the heart, skeletal muscle, bone, liver, and the brain. Thyroid hormone augments adrenergic signaling and influences the signaling of nutrient receptors, such as liver X receptor and peroxisome proliferator-activated receptor alpha and gamma. The major functional thyroid diseases are reduced thyroid hormone production, hypothyroidism, and excess thyroid hormone production, hyperthyroidism. There are rare genetic defects of thyroid hormone signaling. Activation of thyroid hormone pathways are being utilized as novel therapeutic targets for several diseases, including obesity, hyperlipidemia, hepatic steatosis and fibrosis, and cardiac diseases.