Permissive role for ornithine decarboxylase and putrescine in the luteinising hormone surge.
Anterior pituitary gland fragments removed from Wistar-derived rats at 10.00 h on pro-oestrus were perifused with Krebs-bicarbonate medium in a column and exposed to hourly volleys of 6 1-min pulses of 10 nM luteinising hormone (LH)-releasing hormone (LHRH). LH release showed a characteristic pattern of prolonged (over 5 h) sensitisation to the releasing hormone, with the response to each volley becoming progressively greater. The addition of 2 mM difluoromethylornithine (DFMO; an inhibitor of ornithine decarboxylase) to the perifusion medium completely inhibited the response to all volleys of LHRH. This effect of DFMO was reversed by the concurrent inclusion of 2 mM putrescine in the medium. Putrescine alone had a small but non-significant enhancing effect on LHRH-induced release, and no significant effect on basal LH release in this system. In a second series of experiments, tissues were loaded with 1-14C-ornithine and the radioactive carbon dioxide released into the medium during the perifusion monitored. Unstimulated pituitary tissues showed constant low levels of carbon dioxide release during 5 h of incubation, but those given hourly volleys of LHRH showed progressively increasing release of radioactivity, which was blocked by the addition of DFMO. No LHRH-stimulated increase in 14CO2 production from 1-14C-ornithine was seen from pituitary tissue removed at 10.00 h on dioestrus. Administration of DFMO (10-100 mg/rat) on the afternoon of pro-oestrus 4 h before the expected peak of the LH surge reduced the magnitude of the subsequent surge and the concentration of the hormone found in the anterior pituitary gland in a dose-related manner. In addition, the concentration of putrescine, but not of spermidine or spermine, was significantly reduced in treated animals (50 mg/rat) at the time of this attenuated surge.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D065108:Ornithine Decarboxylase Inhibitors; D013096:Spermine; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine