Degradation of luteinizing hormone-releasing hormone (LHRH) and an LHRH agonist by the rat testis.
Degradation of LHRH and [D-Ser(tBu)6,des-Gly-NH10(2)]LHRH ethylamide (LHRH-A), during incubation with high-speed supernatants of rat testes, as assessed by reversed-phase (RP)-HPLC fractionation of the iodinated peptides and by radioimmunoassays for LHRH or LHRH-A, was principally due to a neutral 43 000 Da peptidase with apparent Km values at 25 degrees C of 0.15 microM for LHRH and 1.19 microM for LHRH-A. The peptidase was inhibited by sulphydryl reagents, TLCK, 1,10-phenanthroline, EDTA, bacitracin, other LHRH analogues, oxytocin, [Lys8]vasopressin and somatostatin. It was predomantly located in seminiferous tubule supernatants (98% of recovered activity), with much lower levels in interstitial fluid (2%), interstitial tissue or testicular particulate fractions (less than 0.8%). Extracts of cultured immature Sertoli cells produced LHRH- and LHRH-A-degradation profiles, as assessed by RP-HPLC, that were identical to those produced by testicular supernatants. Similar levels of peptidase activity/mg protein were observed in immature and adult rat testes. These studies indicate that the principal LHRH-peptidase in the rat testis is produced by cells of the seminiferous epithelium, chiefly the Sertoli cell, and may play an important role in regulating the activity of LHRH and other peptide hormones in the testis.
D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism*; D006358:Hot Temperature; D007700:Kinetics; D008297:Male; D015260:Neprilysin; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000201:enzymology* / Q000254:growth & development; D014018:Tissue Distribution; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D011480:Protease Inhibitors; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C019176:Tryptal; D010450:Endopeptidases; D015260:Neprilysin