What it is
TRH is a peptide of three amino acids — pyroglutamic acid, histidine and prolinamide. Written in the shorthand chemists use, it is pGlu-His-Pro-NH2: formula C16H22N6O4, molecular weight 362.38 (PubChem CID 638678). Both ends are capped. The first residue, glutamine, has closed into a ring (pyroglutamic acid), and the last, proline, carries an amide where a free acid would normally be.
The body does not make TRH directly. The hypothalamus makes a 242-residue precursor, pro-TRH, which carries six copies of the TRH sequence in the human version (UniProt P20396); enzymes cut each copy out and finish it into the active tripeptide. One gene, read once, yields six hormone molecules.
What it does
TRH is the top of the hypothalamic–pituitary–thyroid axis. Released from the hypothalamus, it reaches the pituitary and triggers release of thyroid-stimulating hormone (TSH) — and, as two 1971 human studies showed, of the milk hormone prolactin as well (PMID 5002718, 5000704); TSH in turn drives the thyroid to make thyroid hormone (UniProt P20396). It is the signal, TSH is the response, thyroid hormone the end product — and it is TSH, not TRH, that routine thyroid blood tests measure.
UniProt also records a second role from hair-follicle research: TRH is expressed in the follicle epithelium and, in those studies, prolonged the growth phase (anagen) of the hair cycle. That is laboratory and tissue evidence; there is no approved hair use, and the evidence rows label it as such.
History
The 1977 Nobel Prize in Physiology or Medicine went half to Roger Guillemin and Andrew Schally "for their discoveries concerning the peptide hormone production of the brain"; the other half went to Rosalyn Yalow for the radioimmunoassay of peptide hormones (nobelprize.org). The Nobel Assembly's press release recounts that the two rival groups — Guillemin's with about 5 million hypothalamic fragments from sheep, Schally's with the same amount from pigs — concentrated on one releasing factor, TRF, and after years of work stood with 1 mg of a pure substance that did one thing: it released TSH. The nature of the hypothalamic factors, the release says, was not established until 1969. The brain's other releasing and inhibiting peptides have their own entries — gonadorelin (GnRH) and somatostatin.
As a medicine
Synthetic TRH is called protirelin. In the US it was approved as a diagnostic agent — injected so that the pituitary's TSH response could be measured — under two brands:
| Product | Company | Application | First approved | Status (Drugs@FDA, 2026-10-15) |
|---|---|---|---|---|
| Thypinone | Abbott | NDA 017638 | 1976-11-05 | Discontinued |
| Thyrel TRH | Ferring | NDA 018087 | 1978-07-18 | Discontinued |
Neither is marketed today, and Drugs@FDA lists no other protirelin application. Where a TRH stimulation test is discussed, the result is interpreted by the ordering clinician; this entry reports the record and does not interpret any result.
What the research record shows
PubMed indexes 15,610 records for thyrotropin-releasing hormone, 208 tagged as randomised controlled trials, and ClinicalTrials.gov lists 29 studies naming it as an intervention (2026-10-15). Most of the trial literature uses TRH as a test or a research probe of the axis rather than as a treatment.
Related reading
TRH is one of the hypothalamus's peptide signals; its neighbours in the library are corticotropin-releasing hormone, gonadorelin (GnRH), sermorelin (a GHRH fragment) and somatostatin. For how its three residues are joined, see the peptide bond.