Thyrotropin-releasing hormone

Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF), thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary. TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans.

Synthesis


TRH is produced by the hypothalamus in medial neurons of the paraventricular nucleus. At the beginning, it is synthesized as a 242-amino acid precursor polypeptide that contains 6 copies of the sequence -Glu-His-Pro-Gly-, flanked by di-basic peptides that are later processed through proteolysis to give the mature TRH molecule.

It travels across the median eminence to the anterior pituitary gland via the hypophyseal portal system where it stimulates the release of thyroid-stimulating hormone from cells called thyrotropes and excess levels inhibit dopamine, which stimulates the release of prolactin, which in turn decreases GnRH.

TRH can also be detected in other areas of the body including the gastrointestinal system and pancreatic islets, as well as in the brain.

History
The sequence of TRH was first determined, and the hormone synthesized, by Roger Guillemin and Andrew V. Schally in 1969. Both parties insisted their labs determined the sequence first: Schally first suggested the possibility in 1966, but abandoned it after Guillemin proposed TRH was not actually a peptide. Guillemin's chemist began concurring with these results in 1969, as NIH threatened to cut off funding for the project, leading both parties to return to work on synthesis.

Schally and Guillemin shared the 1977 Nobel Prize in Medicine "for their discoveries concerning the peptide hormone production of the brain." News accounts of their work often focused on their "fierce competition" and use of a very large amount of sheep and pig brains to locate the hormone.

Chemical properties
Its molecular weight is 359.5 Da. Its tripeptide structure is: (pyro)Glu-His-Pro-NH2

Clinical significance
It is used in pharmacology (brand name Relefact TRH) to test the response of the anterior pituitary gland.

Medical preparations of TRH are used in diagnostic tests of thyroid disorders and in acromegaly.

A TRH test may be indicated if secondary hypothyroidism is suspected.

Related peptides
TRH belongs to a family of several thyrotropin-releasing hormones (TRH).