Thyrotropin-releasing hormone (TRH) is a tripeptide (L-pyroglutamyl-L-histidinyl-L-proline amide) that is released from the hypothalamus to stimulate release of thyroid-stimulating hormone from the thyrotropes of the anterior pituitary. In addition, TRH is synthesized in other regions of the CNS, where it appears to function as a neuromodulator to influence arousal, cognition, motor activity, depression, and food and water intake. TRH functions in the autonomic nervous system to modulate gastrointestinal motility and acid secretion. The biological functions of TRH are mediated by binding to two Gq-coupled seven transmembrane receptors, TRH1 and TRH2. TRH1 is present in humans, rodents, and other vertebrates, whereas TRH2 has been identified only in rodents. Synthetic TRH (protirelin) is used clinically to evaluate the functionality of the hypothalamic-pituitary-thyroid axis.