Processing of prothyrotropin-releasing hormone (Pro-TRH) by bovine intermediate lobe secretory vesicle membrane PC1 and PC2 enzymes

Deficiencies in Pro-thyrotropin-releasing Hormone Processing and Abnormalities in Thermoregulation in CpeMice

“…Synthetic TRH and TRH-[Gly 4 ] (Peninsula Laboratories, Belmont, CA) were iodinated by the chloramine-T method (17), and the RIAs were performed as described (18 were added in a 0.1-ml aliquot and incubated for 24 h at 4°C. On the third day, anti-guinea pig sera (1:25 dilution) were added as a 0.1-ml aliquot and incubated for 24 h at 4°C.…”

Cellular colocalization and coregulation between hypothalamic pro-TRH and prohormone convertases in hypothyroidism

“…Our laboratories have used biochemical techniques to understand the initial posttranslational modifications of the pro-TRH precursor. We found that the initial cleavages at paired basic residues were primarily by PC1/3 and secondarily by PC2 (9,25,26,35). The intermediate products of pro-TRH generated from these enzymatic cleavages are further modified by exopeptidases, such as CPE or CPD, to remove the carboxyterminal basic amino acids (28) and then amidation at their carboxyl terminus by the action of peptidylglycine ␣-amidating monooxygenase enzyme (6) to generate TRH (pGlu-His-Pro-NH 2 ; thyroliberin).…”

Prohormone-Convertase 1 Processing Enhances Post-Golgi Sorting of Prothyrotropin-releasing Hormone-derived Peptides

“…Scientific debate continues as to what targets prohormones and other proteins into the regulated secretory pathway with some favoring a receptor-mediated model (6 -8), self-aggregation of regulated secretory pathway cargo (9 -11), or binding of the prohormone to lipid rafts (12-14), but it is generally agreed that there are unique structural elements of prohormones, not necessarily universal, that result in their targeting to the regulated secretory pathway (15)(16)(17)(18)(19)(20)(21)(22). It has yet to be reported which elements of pro-TRH might be important in the targeting of this important prohormone to the regulated secretory pathway.Rat pro-TRH is a prohormone composed of 255 amino acids, and when fully processed by prohormone convertases 1 and 2 (PC1 and PC2) yields five molecules of TRH and up to nine other peptides (2,(23)(24)(25). For a number of years TRH was the only peptide derived from pro-TRH known to behave as a hormone, but recent work has demonstrated that the other peptides derived from pro-TRH may have physiological function (26).…”