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Trh analog with carboxyl terminal thioamide group rapid degradation by plasma and its biological effects

, : Trh analog with carboxyl terminal thioamide group rapid degradation by plasma and its biological effects. Endocrinologia Experimentalis 19(4): 213-219

L-pyroglutamyl-L-histidyl-L-proline thioamide - ([Prot3]TRH), a new TRH analogue, has been previously found to have the same binding affinity to adenopituitary receptors as well as TSH and .alpha.-MSH releasing activities as native TRH. In this paper we report also the same time course of TSH response after i.p. injection of this compound (10 .mu.g kg-1) to rats. Binding affinity to specific receptors in rat amygdala, cortex (frontal lobes), hypothalamus, striatum (order according to decreasing affinity) of both peptides was also similar. In contrast to TRH, however, [Prot3]TRH in doses 0.5 and 5 mg kg-1 i.p. did not affect sleeping time and breathing frequency in the rats during barbiturate anaesthesia. Surprisingly, human plasma degraded the new analogue much faster (T1/2 8.5 min) than native TRH (T1/2 30 min). [Prot3]TRH was also degraded faster in plasma of adult rats. Plasma of 6-day-old rat pups failed to degraded both peptides. It was concluded that the substitution of proline amide, for proline thioamide group in TRH molecule did not change binding affinity to receptors to the central nervous system, but decreased biological effectiveness in CNS and substantially decreased the resistance to degradation in human and rat plasma.

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