Concentrations of thyrotropin-releasing hormone (TRH) and deamido-TRH, and TRH deamidase activity in brain.

Abstract

Chromatographic evidence for alternative pathways of TRH catabolism in the brain, involving either cleavage of the pGlu-His peptide bond or deamidation to form pGlu-His- Pro (TRH-OH), has been described. In the present study, RIAs for TRH and TRH-OH were used to determine if synthetic TRH is degraded by rodent brain tissue into TRH-OH and to evaluate the relative rates of TRH and TRH-OH degradation and the concentrations of these two peptides in the brain. Incubation of the 27,000 × g supernatant of rodent brain tissue with synthetic TRH resulted in the formation of TRHOH, which, under high TRH substrate conditions, was a function of the amount of brain tissue present. Treatment of normal rats and hamster with pharmacological doses of T4 for 1 week did not significantly affect brain TRH deamidase activity. Under the in vitro conditions used, the rate of degradation of TRH was 487 ± 36 pg/min compared to 195 ± 31 pg/min for TRH-OH (P < 0.001). Despite the fact that TRH degradation was faster than TRH-OH degradation in the brain, the content of TRH-OH in regions of the brain was usually less than that of TRH and was often undetectable (<0.52 ng/lextract). These data, while confirming the presence of a TRH deamidase in the brain, are compatible with the hypothesis that the percentage of TRH produced in the brain which undergoes deamidation in the brain in vivo is small.