CYCLOOXYGENASE EXPRESS & PROSTAGLANDIN PRODUCT BY PRIMAT PERIOVULATORY FOLLICLES

环加氧酶快递

• 批准号: 6116158
• 负责人: Diane M Duffy
• 金额: $ 9.03万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116158
• 关键词: Mammalia; animal tissue; clinical research; endocrine gland /system; enzymes; hormones; nucleic acids; pharmacology; reproductive system; women's health

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).

由卵巢颗粒细胞产生的前列腺素（PGs） 排卵期卵泡在排卵后迅速增加， 在非灵长类动物中，促性腺激素激增，但这种关系并没有被发现。 在猴子和女人身上做了实验。 检查灵长类动物的PG产生 排卵期卵泡，成年雌性恒河猴接受 促性腺激素促进多卵泡发育。 颗粒 分别于造模前（0 h）和造模后12、24或 促性腺激素促排卵推注给药后36小时 （hCG）。 分析颗粒细胞的mRNA含量， 环氧合酶（考克斯）亚型考克斯-1和考克斯-2，其催化 PG生产的限制步骤。 而颗粒细胞考克斯-1 mRNA 考克斯-2 mRNA水平在围排卵期无变化， 表达在0 h时较低，到12 h时上升40倍，并保持升高 至36 h。卵泡液PGE 2和PGF 2？ 水平也很低， 0 h，并在24 h内保持较低水平。什么是PGE 2和PGF 2？ 浓度在36 h时升高，代表100倍增加 卵泡液水平在24和36小时之间。这些数据表明 排卵期促性腺激素激增增加了灵长类颗粒细胞 通过增强考克斯-2的表达， 卵泡PG水平4-16小时前排卵的预期时间。 为了确定排卵促性腺激素峰是否直接作用于 颗粒细胞刺激考克斯-2表达和PG合成， 排卵剂量给药前获得的颗粒细胞 hCG的培养不含或含排卵浓度的 促性腺激素36小时 促性腺激素不能促进PG的产生 或考克斯-2 mRNA水平高于对照培养物，尽管水平较低 考克斯-1的表达。 因此， 排卵期猴卵泡液前列腺素升高支持 统一的假设是，PG水平升高约10小时前， 排卵对于卵泡破裂和卵母细胞的释放至关重要 在灵长类动物和非灵长类动物物种中。 然而，促性腺激素可能 不直接作用于颗粒细胞刺激PG的产生， 对排卵高峰的反应。 这些研究对两者都适用。 治疗导致不孕的疾病以及 开发新的避孕药来阻止排卵。 资金 俄勒冈州医学研究基金会，HD20869，HD 18185出版物 Duffy DM，Stouffer RL. 环氧合酶表达与前列腺素 排卵周期的生产控制 灵长类的生物钟 排卵演变国际研讨会 和临床概念（在犹他湖城举行，9月24日至27日， 1998），第33页（摘要#2）。 Duffy DM，Stouffer RL. 表达 灵长类卵泡颗粒细胞环氧合酶-1和-2基因 对排卵期促性腺激素激增的反应 内分泌学会 计划和摘要第80届年会（在路易斯安那州新奥尔良举行， June 24-27，1998），第184页（摘要#P1-305）。