Nuclear progesterone receptor is involved in the LH-induced expression of Ptger4b, a prostaglandin E_2 receptor indispensable for ovulation of the medaka

摘要

Ovulation is the process by which one or more viable oocytes are shed from mature ovarian follicles of the ovary in response to the surge of leuteinizing hormone (LH). This process is accomplished by the coordinated actions of many proteins and enzymes, some of which are drastically induced by the gonadotropin. Prosataglandins (PGs) are a group of animal hormones and exhibit a variety of biological activities by binding to their respective receptors. PGs have been implicated in the ovulatory process of a wide variety of vertebrate aniimals. We previously reported that a prostaglandin E_2 receptor subtype EP4b (Ptger4b) plays a role in medaka ovulation and that ptger4b mRNA is drastically induced in the preovulatory follicles at ovulation. In the present study, we focused on the hormonal regulation of ptger4b mRNA expression using this non-mammalian vertebrate model. In vitro incubation of the preovulatory follicle, which had not yet undergone a surge of luteinizing hormone (Lh) in vivo, with medaka recombinant Lh induced expression of ptger4b mRNA. The expression of ptger4b mRNA was found to be inhibited by trilostane, a specific inhibitor of 3(3-hydroxysteroid dehydrogenase. The inhibitory effect of the inhibitor on ptger4b mRNA expression was nullified by adding 17a, 20(3-dihydroxy-4-pregbeb-3-one (DHP), which is well known as maturation-inducing hormone (MIH) in medaka, suggesting a role of progestin in the expression of ptger4b mRNA. Two types of progestin receptors, membrane progestin receptors (mPRs) and nuclear PR (nPR), were found to be expressed in the medaka ovary. Among those, only nPR was induced by medaka recombinant Lh in the follicle and its expression preceded ptger4b mRNA expression. The expression of ptger4b mRNA in the follicle was significantly suppressed by RU486 (also known as mifepristone), which is known to exhibit anti-progestin activity. These results indicate that ptger4b expression is regulated by genomic mechanism involving nPR.