CYCLOOXYGENASE EXPRESS & PROSTAGLANDIN PRODUCT BY PRIMAT PERIOVULATORY FOLLICLES

沙门氏菌颗粒细胞产生前列腺素的研究 排卵后，排卵周卵泡迅速增加 促性腺激素在非灵长类动物中激增，但这种关系尚未得到 在猴子或女人身上进行检查。灵长类生产PG的检测 排卵周卵泡，成年雌性恒河猴 促性腺激素促进多个卵泡发育。颗粒 分别于(0h)、12、24、或 在注射促性腺激素排卵剂后36小时 (HCG)。分析颗粒细胞中mRNAs的含量 环氧合酶(COX)的亚型是COX-1和COX-2，它们催化着 PG生产中的限制步骤。颗粒细胞COX-1mRNA 在排卵期间，COX-2mRNA的水平没有变化 表达在0h时很低，到12h时增加40倍，并保持高水平 卵泡液PGE2和PGF2？水平也很低，在 PGE_2和PGF_2在0小时和24小时维持在低水平。 在36小时内浓度升高，即增加了100倍 卵泡液水平在24到36小时之间。这些数据表明 排卵期促性腺激素激增增加灵长类颗粒细胞 通过增强COX-2的表达来产生PG，导致 卵泡PG水平比预期排卵时间提前4-16小时。 为了确定排卵性促性腺激素激增是否直接作用于 颗粒细胞刺激COX-2表达和PG合成， 应用排卵剂前获取的颗粒细胞 培养的人绒毛膜促性腺激素不含或含有排卵浓度。 促性腺激素36小时。促性腺激素不能促进PG的产生 或COX-2mRNA水平高于对照培养，尽管水平较低 COX-1表达维持不变。因此，这一事件的时机 猕猴排卵期卵泡液中PGs的升高支持 统一的假设是大约10小时前血糖水平升高 排卵是卵泡破裂和卵母细胞释放的关键。 在灵长类和非灵长类物种中。然而，促性腺激素可能 不直接作用于颗粒细胞刺激前列腺素的产生 对排卵激增的反应。这些研究都适用于这两种情况 导致不孕不育的疾病的治疗以及 开发阻止排卵的新型避孕药。资金来源 俄勒冈州医学研究基金会，HD20869，HD18185出版物 Duffy DM，Stouffer RL.环氧合酶表达与前列腺素 排卵周期中的产卵控制排卵 在灵长类动物中打卡。在排卵进化国际研讨会上 和临床概念(9月24-27日在德克萨斯州盐湖城举行， 1998)，第33页(摘要2)。Duffy DM，Stouffer RL.的表达 灵长类卵泡颗粒细胞中环氧合酶-1和-2基因的表达 对排卵期促性腺激素激增的反应。在内分泌学会 第80届年会(在洛杉矶新奥尔良举行， 1998年6月24日至27日)，第184页(摘要#P1-305)。

Production of prostaglandins (PGs) by granulosa cells of periovulatory follicles increases rapidly following the ovulatory gonadotropin surge in nonprimates, but this relationship has not been examined in monkeys or women. To examine PG production by primate periovulatory follicles, adult female rhesus monkeys received gonadotropins to promote multiple follicular development. Granulosa cells and follicular fluid were obtained before (0 h) and 12, 24, or 36 hours after administration of an ovulatory bolus of gonadotropin (hCG). Granulosa cells were analyzed for content of mRNAs for the cyclooxygenase (COX) isoforms COX-1 and COX-2, which catalyze the rate limiting step in PG production. While granulosa cell COX-1 mRNA levels did not change during the periovulatory interval, COX-2 mRNA expression was low at 0 h, rose 40-fold by 12 h, and remained elevated through 36 h. Follicular fluid PGE2 and PGF2? levels were also low at 0 h and remained low through 24 h. How ever , PGE2 and PGF2? concentrations were elevated at 36 h, representing a 100-fold increase in follicular fluid levels between 24 and 36 h. These data suggest that the ovulatory gonadotropin surge increases primate granulosa cell PG production by enhancing COX-2 expression, resulting in elevated follicular PG levels 4-16 hours before the expected time of ovulation. To determine if the ovulatory gonadotropin surge acts directly at granulosa cells to stimulate COX-2 expression and PG synthesis, granulosa cells obtained before administration of the ovulatory dose of hCG were cultured without or with ovulatory concentrations of gonadotropin for 36 hours. Gonadotropin did not enhance PG production or COX-2 mRNA levels above that in control cultures, though low levels of COX-1 expression were maintained. Thus, the timing of the periovulatory rise in follicular fluid PGs in monkeys supports the unifying hypothesis that elevated PG levels about 10 hours before ovulation are critical for follic le rupture and release of the oocyte in primate as well as non-primate species. However, gonadotropin may not act directly at granulosa cells to stimulate PG production in response to the ovulatory surge. These studies are applicable to both the treatment of conditions contributing to infertility as well as the development of novel contraceptives that block ovulation. FUNDING Medical Research Foundation of Oregon, HD20869, HD18185 PUBLICATIONS Duffy DM, Stouffer RL. Cyclooxygenase expression and prostaglandin production during the periovulatory interval Control of the ovulatory clock in primates. In International Symposium on Ovulation Evolving and Clinical Concepts (held in Salt Lake City, UT, September 24-27, 1998), p 33 (abstract #2). Duffy DM, Stouffer RL. Expression of cyclooxygenase-1 and -2 genes in granulosa cells of primate follicles in response to the ovulatory gonadotropin surge. In Endocrine Society Program and Abstracts 80th Annual Meeting (held in New Orleans, LA, June 24-27, 1998), p 184 (abstract #P1-305).