CYCLOOXYGENASE EXPRESS & PROSTAGLANDIN PRODUCT BY PRIMAT PERIOVULATORY FOLLICLES

环加氧酶快递

• 批准号: 6453694
• 负责人: Diane M Duffy
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453694
• 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).

由颗粒细胞生产前列腺素（PGS） 排卵后卵泡周围的卵泡迅速增加 非植物中的促性腺激素激增，但这种关系尚未 在猴子或妇女中检查。 通过灵长类动物检查PG生产 卵泡周围的卵泡，成年雌性恒河猴收到 促性腺激素促进多种卵泡发育。 颗粒 在（0 h）和12、24或 给药后36小时的促性腺激素排卵推注 （HCG）。 分析颗粒细胞的mRNA含量 环氧酶（COX）同工型COX-1和COX-2，它们催化速率 限制PG生产的步骤。 而颗粒细胞Cox-1 mRNA 在卵形间隔内没有变化的水平COX-2 mRNA 表达在0小时时较低，上升40倍到12小时，并保持升高 通过36小时。卵泡液PGE2和PGF2？ 水平也很低 0小时，至24小时保持低位。曾经，PGE2和PGF2？ 浓度在36小时升高，代表100倍 在24至36小时之间的卵泡流体水平。这些数据暗示 排卵性促性腺激素激增会增加灵长类动物颗粒细胞 通过增强COX-2表达来产生PG，导致升高 卵泡PG在预期排卵时间前4-16小时水平。 确定排卵性促性腺激素激增是否直接起作用 颗粒细胞刺激Cox-2表达和PG合成， 在服用排卵剂量之前获得的颗粒细胞 没有或具有排卵浓度的HCG培养 促性腺激素36小时。 促性腺激素没有增强PG产生 尽管低水平 维持COX-1的表达。 因此， 猴子卵泡液PGS的卵巢升高支持 统一的假设，即在10小时前提高了PG水平 排卵对于卵泡破裂和卵母细胞的释放至关重要 在灵长类动物和非成就中。 但是，促性腺激素可能 不直接在颗粒细胞上起作用以刺激PG产生 对排卵激增的反应。 这些研究适用于两者 造成不育以及 开发阻断排卵的新型避孕药。 资金 俄勒冈州医学研究基金会，HD20869，HD18185出版物 Duffy DM，Stouffer RL。 环氧酶表达和前列腺素 排卵间隔期间的产量在排卵间隔内 灵长类动物的时钟。 在排卵的国际研讨会上 和临床概念（9月24日至27日在犹他州盐湖城举行， 1998），第33页（摘要＃2）。 Duffy DM，Stouffer RL。 表达 灵长类动物卵泡颗粒细胞中的环氧合酶-1和-2基因 响应排卵性促性腺激素激增。 在内分泌社会中 计划和摘要第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）。