Ovarian function in the rat following irreversible inhibition of L-ornithine decarboxylase

Abstract

The possibility that the transient rise in rat ovarian ornithine decarboxylase (ODC) activity and the associated increase in putrescine which occur under luteinizing hormone control late in proestrus have an essential role in ovarian function has been tested using DL-α-difluoromethylornithine (DFMO) an irreversible inhibitor of ODC. Treatment with DFMO, 500 mg/kg s.c. at 12:00 h on the day of proestrus and 200 mg/kg, 6, 12 and 18 h thereafter completely suppressed both the rise in ovarian ODC activity and the associated increase in putrescine concentrations. However, ovulation took place normally under these conditions and the course of the resulting pregnancies was also normal. Similarly, combined treatment with DFMO and an inhibitor of S-adenosyl-L-methionine decarboxylase, 1,1-((methylethanediylidine)-dinitrilo) bis (3-aminoguanidine), 25 mg/kg, given at 10:00 h on the morning of proestrus failed to influence either ovulation or the subsequent period of gestation. These data provide no support for a functional role of the pre-ovulatory rise of ODC in rat ovary in the major peri-ovulatory events of that particular cycle, although they do not exclude effects on systems (e.g. steroidogenesis) not directly examined with our experimental approach. On the other hand, inhibition of ODC resulted in an increase in the number of uterine implantation sites following mating at the next proestrusestrus 4 days later. These data would support the previously expressed view that ODC may be associated with the gonadotrophin-induced initiation of follicular development for ovulation in the succeeding cycle. Moreover, since inhibition of the enzyme resulted in facilitation of the process, the normal physiological function of ODC, and/or the putrescine generated through its action, would appear to be inhibitory.