Microsomal prostaglandin E synthase-1 (mPGES-1) is the primary form of PGES expressed by the primate periovulatory follicle

Abstract

Prostaglandin E2 (PGE2) has been identified as the key ovulatory PG in the primate follicle. Follicular PGE2 levels increase just before the expected time of ovulation, suggesting that the midcycle LH surge induces the expression of enzymes involved in PGE2 synthesis. To identify the specific form(s) of prostaglandin E synthase (PGES) expressed by the primate periovulatory follicle, we examined granulosa and theca cell expression of the three microsomal (m) and cytosolic (c) forms of PGES (mPGES-1, mPGES-2 and cPGES) identified to date. Monkey granulosa cells and whole monkey ovaries were obtained from animals receiving exogenous gonadotropins to stimulate multiple follicular development; monkeys then received an ovulatory dose of HCG to initiate periovulatory events. Expression of mPGES-1 mRNA and protein by granulosa cells of periovulatory follicles increased in response to HCG administration, peaking just before the expected time of ovulation. Immunocytochemistry showed that mPGES-1 protein was present in both granulosa and theca cells of monkey periovulatory follicles. Monkey granulosa cells also expressed mPGES-2 and cPGES mRNA, but mRNA levels did not change in response to HCG administration. Isolated monkey theca cells expressed both mPGES-1 and cyclooxygenase-2 mRNA, and produced PGE2 in vitro. Human granulosa-lutein cells obtained from women undergoing treatment for infertility expressed mRNAs for mPGES-1, mPGES-2 and cPGES. These data indicate that mPGES-1 is a gonadotropin-regulated PG synthesis enzyme expressed by granulosa cells of primate periovulatory follicles and suggest that mPGES-1 may be the primary PGES responsible for the increased follicular PGE2 levels necessary for primate ovulation.