Human Reproduction Update Advance Access originally published online on June 17, 2004
Human Reproduction Update 2004 10(5):373-385; doi:10.1093/humupd/dmh032
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Cyclooxygenase-2 and its role in ovulation: a 2004 account
1 Centre de recherche en reproduction animale and Département de biomédecine vétérinaire and 2 Département de pathologie et microbiologie vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, Québec, Canada J2S 7C6
3 To whom correspondence should be addressed: Dr Jean Sirois, Faculté de médecine vétérinaire, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, Québec, Canada J2S 7C6. Email: jean.sirois{at}umontreal.ca
The pre-ovulatory surge of gonadotrophins triggers a marked and obligatory increase in follicular prostaglandin synthesis prior to ovulation, and the cyclooxygenase (COX) enzyme is a key rate-limiting step in the biosynthesis of prostaglandins. In the early 1990s, the pre-ovulatory rise in follicular prostaglandin synthesis was shown to result from the selective induction of a novel COX isoform, now referred to as COX-2. Differences in the time-course of COX-2 induction in species with a short versus a long ovulatory process suggest that the enzyme could be a molecular determinant that sets the alarm of the mammalian ovulatory clock. Some of the fine molecular mechanisms involved in the transcriptional activation of the COX-2 gene in granulosa cells have also been elucidated. The binding of trans-activating upstream stimulatory factors (USF) to a consensus E-box cis-element in the proximal region of the promoter was shown to play a predominant role in COX-2 transcription. Studies showed that COX-2 expression could also serve as a valuable marker for follicular commitment to ovulation during hyperstimulatory cycles. This paper presents a comprehensive review of the events that led to the characterization of COX-2 in pre-ovulatory follicles, updates current concepts on the control of COX-2 expression in pre-ovulatory follicles, and addresses the consequences of COX-2 inhibition to women fertility and potential implications of COX-2 expression in ovarian cancer.
Key words: cyclooxygenase-2 / granulosa cells / ovary / ovulation / prostaglandins
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