Extending the interval of action and effectiveness of the emergency contraceptive ulipristal acetate
Awarded 2013
Large Research Grants
Jon Hennebold, PhD
Oregon Health & Science University

The objective of this project includes determining if the ovarian follicle possesses the capacity to limit the effectiveness of the emergency contraceptive ulipristal acetate (UPA) through the expression of the drug metabolizing enzyme cytochrome P450 3A5 (CYP3A5). Studies conducted through the period of support provided by this SFP Research Fund award included determining the level and regulation of CYP3A5 mRNA expression as well as protein immunolocalization in the rhesus macaque follicle prior to and after an ovulatory stimulus, as well as in the corpus luteum during its development, function and regression. CYP3A5 mRNA expression increased in the follicle from low levels prior to an ovulatory stimulus and again during the development of the corpus luteum. A parallel increase in CYP3A5 immunostaining was observed in the macaque follicle after an ovulatory stimulus and in the large luteal cells of the newly formed corpus luteum. Experiments were also performed whereby recombinant CYP3A5 protein was utilized to show it possesses the capacity to directly metabolize UPA to the biologically inactive di-desmethyl UPA. Collectively, the data obtained through the support of this SFP Research Grant demonstrate that the primate follicle and corpus luteum possesses the UPA metabolizing enzyme CYP3A5, which likely limits the ability of this emergency contraceptive to block ovarian activities that are critical for fertility after the ovulatory midcycle surge of luteinizing hormone.