Thyrotropin-releasing hormone (TRH) is the first hypothalamic hypophysiotropic neuropeptide whose sequence has been chemically characterized. The primary structure of TRH (pGlu-His-Pro-NH(2)) has been fully conserved across the vertebrate phylum. TRH is generated from a large precursor protein that contains multiple repeats of the TRH progenitor tetrapeptide Gln-His-Pro-Gly. In all tetrapods, TRH-expressing neurons located in the hypothalamus project towards the external zone of the median eminence. TRH has an important role in the regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation. TRH causes a variety of thyroidal and non-thyroidal effects, the best known being the feedback regulation of thyroid hormone levels. TRH controls energy homeostasis mainly through its Hypophysiotropic Actions to regulate circulating thyroid hormone levels.