Duffy Diane M, Seachord Carrie L, Dozier Brandy L
Department of Physiological Sciences, Eastern Virginia Medical School, 700 Olney Road, Lewis Hall, Norfolk, VA 23507, USA.
Hum Reprod. 2005 Jun;20(6):1485-92. doi: 10.1093/humrep/deh784. Epub 2005 Mar 17.
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.
前列腺素E2(PGE2)已被确定为灵长类动物卵泡中关键的排卵前列腺素。卵泡PGE2水平在预期排卵时间前升高,提示月经周期中期促黄体生成素峰诱导参与PGE2合成的酶表达。
为鉴定灵长类动物排卵周围卵泡表达的前列腺素E合酶(PGES)的特定形式,我们检测了迄今已鉴定的三种微粒体(m)和胞质(c)形式的PGES(mPGES-1、mPGES-2和cPGES)在颗粒细胞和卵泡膜细胞中的表达。从接受外源性促性腺激素刺激多个卵泡发育的动物获取猴颗粒细胞和整个猴卵巢;然后给猴子注射排卵剂量的人绒毛膜促性腺激素以启动排卵周围事件。
排卵周围卵泡颗粒细胞中mPGES-1 mRNA和蛋白表达在给予人绒毛膜促性腺激素后增加,在预期排卵时间前达到峰值。免疫细胞化学显示mPGES-1蛋白存在于猴排卵周围卵泡的颗粒细胞和卵泡膜细胞中。猴颗粒细胞也表达mPGES-2和cPGES mRNA,但mRNA水平在给予人绒毛膜促性腺激素后未发生变化。分离的猴卵泡膜细胞表达mPGES-1和环氧化酶-2 mRNA,并在体外产生PGE2。从不育症治疗女性获取的人颗粒黄体细胞表达mPGES-1、mPGES-2和cPGES的mRNA。
这些数据表明mPGES-1是一种受促性腺激素调节的PG合成酶,由灵长类动物排卵周围卵泡的颗粒细胞表达,并提示mPGES-1可能是负责灵长类动物排卵所需卵泡PGE2水平升高的主要PGES。