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).

颗粒细胞产生前列腺素（PG） 排卵期卵泡在排卵后迅速增大 非灵长类动物中促性腺激素激增，但这种关系尚未得到证实 在猴子或女性身上进行了检查。 检查灵长类动物的 PG 产生 成年雌性恒河猴的排卵期卵泡 促性腺激素促进多个卵泡发育。 颗粒状 细胞和卵泡液在（0小时）和12、24或之前获得 促性腺激素排卵推注后 36 小时 （人绒毛膜促性腺激素）。 分析颗粒细胞的 mRNA 含量 环加氧酶 (COX) 同工型 COX-1 和 COX-2，催化速率 限制PG生产的步骤。 而颗粒细胞 COX-1 mRNA COX-2 mRNA 水平在围排卵间隔期间没有变化 0小时时表达量较低，12小时时表达量上升40倍，并保持升高状态 到 36 小时。卵泡液PGE2和PGF2？ 水平也较低 0 小时并在 24 小时内保持较低水平。 PGE2和PGF2怎么样？ 36小时浓度升高，增加了100倍 24 至 36 小时之间的卵泡液水平。这些数据表明 排卵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，从而导致 预计排卵时间前 4-16 小时的卵泡 PG 水平。 确定排卵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， 施用排卵剂量之前获得的颗粒细胞 的 hCG 在没有排卵浓度或有排卵浓度的情况下进行培养 促性腺激素36小时。 促性腺激素不会增加 PG 的产生 或 COX-2 mRNA 水平高于对照培养物中的水平，尽管水平较低 COX-1 的表达得以维持。 因此，时间安排 猴子卵泡液 PG 的围排卵升高支持 统一的假设是，大约 10 小时前 PG 水平升高 排卵对于卵泡破裂和卵母细胞释放至关重要 在灵长类动物和非灵长类动物中。 然而，促性腺激素可能 不直接作用于颗粒细胞刺激 PG 产生 对排卵激增的反应。 这些研究同时适用于 治疗导致不孕症的疾病以及 开发阻止排卵的新型避孕药。 资金 俄勒冈州医学研究基金会，HD20869、HD18185 出版物 达菲 DM，斯托弗 RL。 环加氧酶表达和前列腺素 围排卵间隔期间的生产 控制排卵 灵长类动物的时钟。 在国际排卵进化研讨会上 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）。 达菲 DM，斯托弗 RL。 表达 灵长类卵泡颗粒细胞中的环氧合酶-1和-2基因 响应排卵促性腺激素激增。 在内分泌学会 议程和摘要第 80 届年会（在路易斯安那州新奥尔良举行， 1998 年 6 月 24-27 日），第 184 页（摘要#P1-305）。