[Reproduction physiology and prostanoids].
Prostanoids, which consist of prostaglandins (PGs) and thromboxane, are produced from arachidonic acid by cyclooxygenases (COXs) as a rate-limiting step, and they exert various biological actions. Classically, prostanoids are suspected to be closely related to female reproductive processes such as ovulation, luteolysis and uterine contraction, as well as pathological processes such as fever generation and pain modulation. Recently the cDNA cloning of a series of prostaglandin-synthesizing enzymes and receptors enabled us to clarify which isoform or subtype is involved in each reproductive process by generating individual gene-deficient mice. In late pregnancy, PGF2 alpha synthesized by COX-1 is essential for induction of parturition via luteolysis. Furthermore, impaired induction of COX-2 in the myometrium of PGF2 alpha receptor-deficient mice is accompanied with loss of parturition, suggesting that COX-2 is presumably responsible for producing uterotonic PGs. In early pregnancy, PGE2 synthesized by COX-2 induces the expansion of cumulus cells through EP2 receptor and contributes to ovulation and fertilization. These results may be useful in not only developing novel drugs in the reproductive area but also understanding and overcoming harmful reproductive side effects of classical and novel drugs in non-reproductive areas.
Tsuboi
K
K
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. ktsuboi@pharm.kyoto-u.ac.jp
Ichikawa
A
A
D000818:Animals; D003001:Cloning, Molecular; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000502:physiology*; D015195:Drug Design; D005260:Female; D005306:Fertilization; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D007743:Labor, Obstetric; D003341:Luteolysis; D008565:Membrane Proteins; D010060:Ovulation; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000502:physiology; D058307:Receptors, Prostaglandin E, EP2 Subtype; D012098:Reproduction / Q000502:physiology*
D007527:Isoenzymes; D008565:Membrane Proteins; C545644:PTGER2 protein, human; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases