Electroconvulsive seizures increase levels of PS4, the TRH-enhancing peptide [prepro-TRH(160-169)], in rat brain

We report the development of a radioimmunoassay for prepro-TRH(160-169) (PS4), a thyrotropin-releasing hormone (TRH) enhancing peptide, and its use in characterizing the effect of electroconvulsive seizures on the levels of this peptide in various brain regions of male Wistar rats. We found that electroconvulsive seizures significantly elevated the PS4 levels in hippocampus, amygdala, pyriform (olfactory) cortex, and anterior cortex but not in striatum, motor cortex, locus ceruleus, or ventral lateral medulla. The levels of PS4 were highly correlated with the corresponding TRH (p-Glu-His-Pro-NH2) and TRH-Gly (p-Glu-His-Pro-Gly) levels in hippocampus, amygdala, and pyriform cortex, consistent with the prepro-TRH source of all of these peptides. The PS4 levels in hippocampus and amygdala were significantly correlated with the immobility time in the Porsolt forced swim test, an established animal model for antidepressant effects. The PS4 levels in peripheral blood, hypothalamus, anterior cortex, amygdala, and eyes increased severalfold at 20 min following intracisternal injection of 228 microg of this peptide, suggesting that it readily crosses the blood-brain barrier. The pituitary levels of PS4 and TRH-Gly, on the other hand, were decreased within 20 min by intracisternal PS4, suggesting PS4 stimulated the release of prepro-TRH peptides from the pituitary. Fresh rat and human serum rapidly degraded PS4, indicating that it may act primarily as a paracrine modulator of TRH effects in pituitary, brain, and reproductive system.