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Influence of Ovarian Ornithine Decarboxylase in Folliculogenesis and Luteinization

Departments of Biochemistry and Molecular Biology (A.J.L.-C., C.L.-G., F.T., R.P.), Pharmacology (C.M.B., A.C.), and Cell Biology (M.T.C.), Faculty of Medicine, University of Murcia, 30100 Murcia, Spain

Address all correspondence and requests for reprints to: Dr. Rafael Peñafiel, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Campus de Espinardo, 30100 Murcia, Spain. E-mail: rapegar{at}um.es.

LH plays a relevant role in folliculogenesis, ovulation, and luteinization. Although ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is a target of LH in the ovary, the functional significance of ODC induction has remained elusive. Our study reveals that the blockade of the induction of ovarian ODC by means of the specific inhibitor -difluoromethylornithine (DFMO) affects folliculogenesis and luteinization. In immature female mice, DFMO was found to inhibit ovarian growth, the formation of Graafian follicles, and the secretion of progesterone and estradiol. In adult cycling females, the administration of DFMO on the evening/night of proestrus markedly decreased plasma progesterone levels at diestrus, which was associated to the decrease in the expression of steroidogenic factor 1, cytochrome cholesterol side chain cleavage enzyme, and steroidogenic acute regulatory protein in the ovary and to a reduced vascularization of the corpora lutea. These effects were not reverted by the administration of gonadotropins or prolactin. ODC immunoreactivity was also stimulated by LH in theca and granulosa cells of antral follicles but not in preantral follicles. Overall, these experiments demonstrate that elevated ODC values found in the ovary of immature and adult mice play a relevant function in ovarian physiology and that ODC/polyamines must be considered as important mediators of some of the effects of LH on follicular development and luteinization.

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