Let’s know about Thyrotropin Releasing Hormone. Thyrotropin Releasing Hormone ( TRH ) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid stimulating hormone (TSH) and prolactin from the anterior pituitary.
TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbances of consciousness in humans. [1] Its drug form is called protirelin.
Synthesis and Release
TRH is synthesized within the parvocellular neurons of the paraventricular nucleus of the hypothalamus. [2] It is translated as a 242-amino acid precursor polypeptide consisting of 6 copies of the sequence—Gln–His–Pro–Gly–, surrounded by Lys–Arg or Arg–Arg sequences.
To produce the mature form, a series of enzymes are required. First, a protease flanking Lys-Arg or Arg-Arg leads to the C-terminal. Second, a carboxypeptidase removes the Lys/Arg residue leaving Gly as a C-terminal residue. Then, this Gly is converted to an amide residue by a series of enzymes known collectively as peptidylglycine-alpha-amidating monooxygenase. Simultaneously with these processing steps, the N-terminal Gln (glutamine) is converted to pyroglutamate (a cyclic residue). These multiple steps generate 6 copies of the mature TRH molecule per precursor molecule for human TRH (5 for mouse TRH).
TRH synthesized neurons of the paraventricular nucleus project into the central part of the outer layer of the median eminence. After secretion at the median eminence, TRH travels through the anterior pituitary to the hypophyseal portal system where it binds to the TRH receptor by stimulating the release of thyroid-stimulating hormone from thyrotropes and prolactin from lactotropes. [3] The half-life of TRH in the blood is approximately 6 minutes.
structure
TRH is a tripeptide, containing the amino acid sequence of pyroglutamyl-histidyl-proline amide.
history
The structure of the TRH was first determined, and in 1969 by Roger Guillemin and Andrew V. Hormones synthesized by Scali. [4] [5] Both sides insisted that their laboratories determined the sequence first: Scali first suggested the possibility in 1966, but abandoned it after TRH proposed by Guillemin that it was not actually a peptide. Guillemin’s chemist began to agree with these results in 1969, as the NIH threatened to cut funding for the project, forcing both sides to return to work on the synthesis. [6]
Schally and Guillemin shared the 1977 Nobel Prize in Medicine “for their discoveries concerning peptide hormone production in the brain” . [7] News articles of his work often focus on their “fierce competition” and the use of an extremely large amount of sheep and pig brains to detect hormones. [6]
clinical significance
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 the TRH test. This is done as a diagnostic test for thyroid disorders such as secondary hypothyroidism and acromegaly.
TRH has anti-depressant and suicidality properties, [8] and in 2012 the US military awarded a research grant to develop a TRH nasal spray to prevent suicide among its ranks.
TRH in rats has been shown to be an anti-aging agent with a broad spectrum of activities which, due to their actions, suggest that TRH has a fundamental role in the regulation of metabolic and hormonal functions. [11 1]
Side effects
Side effects following intravenous TRH administration are minimal. [12] Nausea, flushing, urinary urgency and a slight increase in blood pressure have been reported. [13] After intrathecal administration, tremors, sweating, tremors, restlessness, and a mild increase in blood pressure were observed.
