Structural formula of TRH
|Locus||Chr. 3 q13.3-q21|
|Mol. mass||362.38367 g/mol|
Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF), thyroliberin or protirelin, is a tropic, tripeptidal hormone, produced by the hypothalamus, that stimulates the release of TSH (thyroid-stimulating hormone) and prolactin from the anterior pituitary. TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans.
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 -Gln-His-Pro-Gly-, flanked by Lys-Arg or Arg-Arg sequences. To produce the mature form, a series of enzymes are required. First, a protease cleaves to the C-terminal side of the flanking Lys-Arg or Arg-Arg. Second, a carboxypeptidase removes the Lys/Arg residues leaving Gly as the C-terminal residue. Then, this Gly is converted into an amide residue by a series of enzymes collectively known as peptidylglycine-alpha-amidating monooxygenase. Concurrently with these processing steps, the N-terminal Gln (glutamine) is converted into pyroglutamate (a cyclic residue). These multiple steps produce 6 copies of the mature TRH molecule per precursor molecule for human TRH (5 for mouse TRH).
Following secretion, TRH 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. Excess levels of TRH inhibit dopamine, resulting in a disinhibition of prolactin (dopamine inhibits prolactin) and a subsequent decrease in GnRH release (prolactin inhibits GnRH).
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.
TRH is used clinically by intravenous injection (brand name Relefact TRH) to test the response of the anterior pituitary gland; this procedure is known as a TRH test. This is done as diagnostic test of thyroid disorders such as secondary hypothyroidism and in acromegaly.
TRH has been shown in mice to be an anti-aging agent with a broad spectrum of activities that, because of their actions, suggest that TRH has a fundamental role in the regulation of metabolic and hormonal functions.
Side effects after intravenous TRH administration are minimal. Nausea, flushing, urinary urgency, and mild rise in blood pressure have been reported. After intrathecal administration, shaking, sweating, shivering, restlessness, and mild rise in blood pressure were observed.
|Thyrotropin-releasing hormone (TRH)|
TRH belongs to a family of several thyrotropin-releasing hormones.
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