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首页> 外文期刊>Endocrinology >Prostaglandin E2 (EP) receptors mediate PGE2-specific events in ovulation and luteinization within primate ovarian follicles
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Prostaglandin E2 (EP) receptors mediate PGE2-specific events in ovulation and luteinization within primate ovarian follicles

机译:前列腺素E2(EP)受体介导灵长类卵巢卵泡排卵和黄体生成过程中PGE2特异性事件

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摘要

Prostaglandin E2 (PGE2) is a key mediator of ovulation. All 4 PGE2 receptors (EP receptors) are expressed in the primate follicle, but the specific role of each EP receptor in ovulatory events is poorly understood. To examine the ovulatory events mediated via these EP receptors, preovulatory monkey follicles were injected with vehicle, the PG synthesis inhibitor indomethacin, or indomethacin plus PGE2. An ovulatory dose of human chorionic gonadotropin was administered; the injected ovary was collected 48 hours later and serially sectioned. Vehicle-injected follicles showed normal ovulatory events, including follicle rupture, absence of an oocyte, and thickening of the granulosa cell layer. Indomethacin-injected follicles did not rupture and contained oocytes surrounded by unexpanded cumulus; granulosa cell hypertrophy did not occur. Follicles injected with indomethacin plus PGE2 were similar to vehicle-injected ovaries, indicating that PGE2 restored the ovulatory changes inhibited by indomethacin. Additional follicles were injected with indomethacin plus an agonist for each EP receptor. EP1, EP2, and EP4 agonists each promoted aspects of follicle rupture, but no single EP agonist recapitulated normal follicle rupture as seen in follicles injected with either vehicle or indomethacin plus PGE2. Although EP4 agonist-injected follicles contained oocytes in unexpanded cumulus, the absence of oocytes in EP1 agonist- and EP2 agonistinjected follicles suggests that these EP receptors promote cumulus expansion. Surprisingly, the EP3 agonist did not stimulate any of these ovulatory changes, despite the high level of EP3 receptor expression in the monkey follicle. Therefore, agonists and antagonists selective for EP1 and EP2 receptors hold the most promise for control of ovulatory events in women.
机译:前列腺素E2(PGE2)是排卵的关键介体。所有4种PGE2受体(EP受体)均在灵长类动物的卵泡中表达,但每种EP受体在排卵事件中的具体作用了解甚少。为了检查通过这些EP受体介导的排卵事件,给排卵前的猴卵泡注射了媒介物,PG合成抑制剂吲哚美辛或吲哚美辛加PGE2。排卵剂量的人绒毛膜促性腺激素; 48小时后收集注射的卵巢并连续切片。媒介物注射的卵泡显示正常的排卵事件,包括卵泡破裂,卵母细胞缺失和颗粒细胞层增厚。消炎痛注射的卵泡未破裂,卵母细胞被未扩张的卵丘包围;没有发生颗粒细胞肥大。吲哚美辛加PGE2注射的卵泡与媒介物注射的卵巢相似,表明PGE2恢复了吲哚美辛抑制的排卵变化。对于每个EP受体,向另外的卵泡注射吲哚美辛加激动剂。 EP1,EP2和EP4激动剂均促进卵泡破裂的各个方面,但没有一个EP激动剂能重现正常的卵泡破裂,如在注射媒介物或消炎痛加PGE2的卵泡中所见。尽管注射EP4激动剂的卵泡中未扩张的卵丘中含有卵母细胞,但注射EP1激动剂和EP2激动剂的卵泡中不存在卵母细胞提示这些EP受体促进卵丘扩张。令人惊讶的是,尽管猴卵泡中EP3受体的表达水平很高,但EP3激动剂并未刺激任何这些排卵变化。因此,对EP1和EP2受体具有选择性的激动剂和拮抗剂具有控制女性排卵事件的最大希望。

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