title: Endopeptidase EC 3.4.24.15 presence in the rat median eminence and hypophysial portal blood and its modulation of the luteinizing hormone surge.
abstract: The endopeptidase EC 3.4.24.15 (EP24.15) is a zinc metalloendopeptidase that is widely distributed in a variety of tissues, including the testes, pituitary and the central nervous system. Among its numerous roles in metabolizing and processing biologically-active peptides, the enzyme degrades gonadotropin-releasing hormone (GnRH) by cleaving the central Tyr5-Gly6 bond. The aim of the present studies was to determine 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 this enzyme is secreted into portal blood. We have also shown a physiological role for this enzyme in that an inhibition of its activity with a specific inhibitor augmented the steroid-induced LH increase in ovariectomized rats. The present results suggest that secretory and post-secretory mechanisms are important in shaping the GnRH signal from the central nervous system; GnRH metabolism by EP24.15 may be one such mechanism.
authors.affiliation: Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Wu
authors.forename: A R
authors.initials: AR
authors.lastname: Pierotti
authors.forename: M
authors.initials: M
authors.lastname: Jakubowski
authors.forename: W J
authors.initials: WJ
authors.lastname: Sheward
authors.forename: M J
authors.initials: MJ
authors.lastname: Glucksman
authors.forename: A I
authors.initials: AI
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: King
authors.forename: G
authors.initials: G
authors.lastname: Fink
authors.forename: J L
authors.initials: JL
authors.lastname: Roberts
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000097:blood*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000098:blood supply*; D011168:Portal System; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D008666:Metalloendopeptidases; C022510:thimet oligopeptidase