Thyrotropin-releasing hormone (TRH), also known as thyroliberin, was the first hypothalamic hypophysiotropic hormone to be isolated and chemically characterized. As a modified tripeptide with the amino acid sequence pyroglutamyl-histidyl-proline amide (pGlu-His-Pro-NH₂), TRH functions as both a neurohormone and a neurotransmitter. Despite its small size, this peptide plays a central role in neuroendocrine regulation and exerts diverse physiological effects throughout the body.

Biosynthesis and Molecular Structure

TRH is synthesized from a larger precursor protein, preproTRH, encoded by a single-copy gene of approximately 2.6 kb comprising three exons. The precursor contains multiple copies of the progenitor sequence Gln-His-Pro-Gly, each flanked by paired basic amino acid residues that serve as cleavage sites for processing enzymes. Following translation, preproTRH undergoes a series of post-translational modifications, including endoproteolytic cleavage, removal of basic residues by carboxypeptidases, C-terminal amidation, and N-terminal cyclization of glutamine to pyroglutamate. These processing steps generate multiple biologically active TRH molecules from a single precursor, with human preproTRH containing six TRH progenitor sequences.

Clinical Applications and Diagnostic Use

The synthetic TRH analogue protirelin has been widely used as a diagnostic agent for evaluating pituitary and thyroid function. The TRH stimulation test assesses the secretory reserve of pituitary TSH and prolactin and assists in distinguishing hypothalamic from pituitary causes of hypothyroidism. Following intravenous administration, TRH exhibits a plasma half-life of approximately five minutes, while circulating TSH concentrations typically reach their maximum levels within 20–30 minutes, providing a reliable assessment of pituitary responsiveness.