CHANGES IN TRH AND ITS DEGRADING ENZYME PYROGLUTAMYL PEPTIDES-II, DURING THE DEVELOPMENT OF AMYGDALOID KINDLING

Pyroglutamyl peptidase II (PPII) is a neuronal ectoenzyme responsible for thyrotropin releasing hormone (TRH) degradation at the synaptic cl eft. PPII, heterogeneously distributed in different brain regions and adenohypophysis, is regulated under various endocrine conditions where TRH is involved in thyrotropin or prolactin regulation but only at th e adenohypophyseal level. TRH can downregulate PPII activity in cultur ed adenohypophyseal cells. TRH present in extrahypothalamic brain area s has been postulated to serve as a neuromodulator and levels of this peptide increase in amygdala, hippocampus and cortex after electrical stimulation (kindling or electroshock). To study whether brain PPII co uld be regulated in conditions that stimulate TRHergic neurons, TRH an d PPII activity were determined during the development of amygdaloid k indling in the rat. TRH levels increased from stage II to V in amygdal a and hippocampus in the ipsi- and contralateral side to stimulation. In n. accumbens a decrease, compared to sham was observed at stage II, but levels raised through stage V. In contrast, PPII activity was inc reased at stage II, in amygdala of both sides and in hippocampus, fron tal cortex, n. accumbens and hypothalamus of the contralateral side; l evels decreased at stage V to sham values in most structures (except a mygdala and hippocampus where the activity was 30% below controls). Th ese results suggest that PPII activity in the central nervous system c an be regulated in conditions known to affect TRHergic neurons.