TRH (thyrotropin-releasing hormone) is a hypothalamic tripeptide that serves as the central component of the hypothalamic-pituitary-thyroid (HPT) axis. As a G-protein coupled receptor ligand, TRH binds to the TRHR receptor on pituitary thyrotroph cells to stimulate TSH secretion, which in turn promotes thyroid hormone synthesis and release 12. TRH-producing neurons are primarily localized in the paraventricular nucleus of the hypothalamus, with additional populations in the suprachiasmatic and sexually dimorphic nuclei 3. Beyond its neuroendocrine role, TRH functions as a neuromodulator throughout the central and peripheral nervous systems 1. The hormone activates phosphoinositide signaling cascades and intracellular calcium mobilization in target cells 14. TRH also modulates immune function by enhancing interferon-gamma production in peripheral blood mononuclear cells 2. Clinically, dysregulation of hypothalamic TRH expression is implicated in nonthyroidal illness syndrome and stress-related thyroid dysfunction 35. Recent evidence indicates TRH protects hypothalamic neurons from inflammatory damage, thereby regulating systemic lipid metabolism through hypothalamic-liver communication 6. Mutations in the TRHR gene cause central hypothyroidism, highlighting the critical importance of TRH signaling in thyroid homeostasis 7.