[Physiological functions of prostanoid receptors and their subtypes]

Prostaglandins exert a wide variety of biological actions through specific receptors. The prostaglandins PGE2 and PGF2 alpha have been suggested to affect many physiological processes. There have been four pharmacologically identified receptor subtypes, EP1 through EP4 for PGE2 and a single receptor type, FP for PGF2 alpha. However, it is yet unknown as to which receptor is involved in each process. To make this clear, we investigated the distribution of these receptors in various systems and established mice deficient in each receptor and examined their physiology. Finally, we found that these receptors are involved in several processes associated with reproduction physiology. FP-deficient mice are able to become pregnant, but cannot deliver their pups because of the lack of parturition; luteolysis does not occur normally. EP2-deficient mice are able to become pregnant, but their litter sizes are much reduced, which is due to defects in ovulation and fertilization; cumulus cell function is impaired. EP4-deficient mice die within a few days after birth because of patency of the ductus arteriosus; remodeling of cardiovascular system during birth is impaired. Thus, the E- and F-types of prostaglandins play roles in cumulus function, luteolysis and ductus closure through EP2, FP and EP4, respectively.