ENDOPEPTIDASE EC-3.4.24.15 PRESENCE IN THE RAT MEDIAN-EMINENCE AND HYPOPHYSEAL PORTAL BLOOD AND ITS MODULATION OF THE LUTEINIZING-HORMONE SURGE

The endopeptidase EC 3.4.24.15 (EP24.15) is a zinc metalloendopeptidas e that is widely distributed in a variety of tissues, including the te stes, pituitary and the central nervous system, Among its numerous rol es in metabolizing and processing biologically-active peptides, the en zyme degrades gonadotropin-releasing hormone (GnRH) by cleaving the ce ntral Tyr(5)-Gly(5) bond. The aim of the present studies was to determ ine whether EP24.15 can modulate the concentrations of GnRH within the hypothalamo-hypophysial portal blood and thereby play a physiological role in reproduction, Our data suggest the presence of immunoreactive EP24.15 in the perivascular space of the median eminence and that thi s enzyme is secreted into portal blood. We have also shown a physiolog ical role for this enzyme in that an inhibition of its activity with a specific inhibitor augmented the steroid-induced LH increase in ovari ectomized rats. The present results suggest that secretory and post-se cretory mechanisms are important in shaping the GnRH signal from the c entral nervous system; GnRH metabolism by EP24.15 may be one such mech anism.