PGlu-Glu-Pro Amide

[Glu2]-TRH tripeptide – pGlu-Glu-Pro-NH2 (CAS: 85541-78-2) Thyrotropin-releasing hormone (TRH) Thyrotropin-releasing hormone (TRH) is a tripeptide hypothalamic regulatory hormone that regulates the release of thyroid-stimulating hormone (TSH), as well as prolactin (for breasts growth and milk production during and after pregnancy) . To obtain thyrotropin-releasing hormones, 6 pro-TRH peptides have first to be obtained from the larger preproTRH precursor (UniProt: P20396) . These octapeptides are then cleaved between Arginine/Glutamine and Glutamine/Lysine residues to release 6 Gln-His-Pro-Gly peptides that will be enzymatically converted in pGln-His-Pro-NH2 peptides (pGln representing pyroglutamine) . After TRH maturation (1) in neurons located in the pituitary gland, the hormone will be transported along axons (2) to reach the hypophyseal portal system via exocytosis (3) . Once the thyrotrophs reached, thyrotropin-releasing hormone binds TRH-receptor (4) to enable TSH synthesis and secretion that will stimulate thyroid follicular cells to produce thyroid hormones Triiodothyronine (T3) and Tetraiodothyronine (T4) . [Glu2]-TRH_pGluGLuPro-NH2_SB-PEPTIDE scheme: TRH metabolism pathway TRH implication in hypothyroidism and cholinergic neuronal activity TRH being directly involved in TSH release, deficiency of this hormone has been found to be related to secondary hypothalamic hypothyroidism. This condition can affect all body functions, causing various symptoms of different severity from fatigue to brittle nails, cold intolerance or joint pain even. On the contrary, even though no case of excessively high levels of TRH was observed up to now, studies showed the cholinergic effect of TRH in mouse brain. In 1991, for instance, M. G. Giovannini & al. associated TRH administration, s.c. or via local perfusion, with acetylcholine (ACh) release increase from rodents’ cortex and hippocampus, which suggested the strong stimulant action of TRH on cortical and hippocampal cholinergic pathways. [Glu2]-TRH tripeptide applications In the last few years, [Glu2]-TRH, or PGPA for pyroglutamyl-glutamyl-proline amide, has been widely studied due to its potential applications in science and medicine. Indeed, this synthetic peptide has been associated with a wide range of biological effects, including anti-inflammatory, antioxidant, and neuroprotective activities. Moreover, low levels of TSH being naturally impacted by deficient production of TRH, analogs with impaired recognition by thyroliberinase, such as [Glu2]-TRH, depicted interesting features to counteract its degradation. As a matter of fact, histidine substitution by glutamic acid in TRH original sequence prevents enzymatic cleavage between the N-terminal pyroglutamyl group and the usual central histidine residue. This metabolically stable synthetic peptide significantly attenuates TRH-induced hippocampal extracellular acetylcholine release, thereby acting as a negative modulator of TRH cholinergic effect in mice brain.