Effect of difluoromethylornithine on the LH surge and subsequent ovulation in the rat.
Female Wistar-derived rats with regular oestrous cycles were injected s.c. at 15.00 h on pro-oestrus with difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase. The drug (10-100 mg/rat) caused a dose-related reduction in the concentration of LH in plasma taken at 19.00 h (the time of the peak of the LH surge in this colony). There was also a dose-related reduction in the pituitary content of total polyamines. The reduction in the plasma concentration of LH was not due to the shifting of the time of the peak of the surge, as concentrations were significantly lower than control from 17.00 to 21.00 h, the overall reduction in total LH release being approximately 50%. The number of ova in the oviducts at 06.00 h next morning was significantly reduced by treatment with 50 mg DFMO/rat, by an average of 70%. Injection of DFMO enhanced the fall in plasma oestradiol concentrations seen between 15.00 and 19.00 h, in a dose-related manner. It also prevented the rise in progesterone concentrations seen in control animals during this period. The ability of DFMO to prevent the rise in plasma concentrations of LH was not secondary to the effects of the drug on ovarian steroid production because DFMO also significantly reduced the LH surge in animals ovariectomized on dioestrus and given appropriate replacement injections of oestradiol and progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D007031:Hypothalamus / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D010902:Pituitary Gland / Q000187:drug effects; D011073:Polyamines / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D011073:Polyamines; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D009955:Ornithine Decarboxylase; D000518:Eflornithine