ENDOMETRIAL EFFECT OF ANTIPROGESTIN RELEAS INTRAUTER DEVICE IN NON HUMAN PRIMATE

抗孕激素释放宫内装置对非人灵长类动物的子宫内膜影响

• 批准号: 6453729
• 负责人: ROBERT M BRENNER
• 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/6453729
• 关键词: Mammalia; bioimaging /biomedical imaging; hormones; imaging /visualization /scanning; model design /development; reproductive system

The goal of this study is to develop an antiprogestin-releasing intrauterine device (IUD), which might be applied as a contraceptive, or to inhibit endometrial bleeding. In collaboration with Leiras OY, Finland, a subsidiary of Schering AG, we tested two types of IUDs that release the new antiprogestin ZK 230 211 (ZK211). One released a high dose (26-30.2 ?g ZK 211/day) and the other a low dose (3.3-4.5 ?g ZK 211/day). Stumptail macaques were originally considered as the most suitable species for this project as they have a cervix that is straight compared to the S-shaped cervix of other common laboratory macaques. However, we had great difficulty in cannulating the cervix of the stumptails and discovered that while the external os and the cervical canal are straight and easy to cannulate, the internal os is extremely small and is itself S-shaped. To provide information relevant to the project goals, high and low dose IUDs were inserted in stumptailed and pig tail ed macaques by hysterectomy. Our first study was designed to test whether antiprogestin IUDs could inhibit the endometrial effects of progesterone. Both the low and high dose IUDs induced menstruation within three days of inserting the IUDs. This indicated that the amount of antiprogestin produced locally by both the high and low dose IUDs was sufficient to prevent systemic progesterone from maintaining the endometrium in a progestational state. The monkeys were treated to induce artificial menstrual cycles and tissues were collected at the end of one cycle. The endometrium exposed to the blank IUD showed no major differences from a typical progestational endometrium, except that the amount of endometrial tissue was somewhat less than would be expected at the end of a normal cycle. The antiprogestin IUDs caused a severe compaction of the stroma and an inhibition of the effects of P on both glandular sacculation and spiral artery development. There was evidence of perivascular hy aline degeneration similar to that observed after long term systemic antiprogestin. These results suggest that acute administration of local antiprogestin by IUD can act to inhibit endometrial development and may represent an alternative to systemic treatment to control endometrial bleeding or as a uterine based contraceptive. FUNDING Lalor Foundation PUBLICATIONS None

本研究的目标是开发一种抗孕激素释放药物 宫内节育器 (IUD)，可用作避孕措施， 或抑制子宫内膜出血。 与 Leiras OY 合作， 芬兰是先灵公司的子公司，我们测试了两种类型的宫内节育器 发布新的抗孕激素 ZK 230 211 (ZK211)。 其中一位发布了高 剂量（26-30.2μg ZK 211/天）和另一个低剂量（3.3-4.5μg ZK 211/天）。 短尾猕猴最初被认为是最 适合该项目的物种，因为它们的子宫颈是 与其他普通实验室的S形宫颈相比，是直的 猕猴。 然而，我们在对子宫颈进行插管时遇到了很大的困难。 的树桩，发现虽然外部操作系统和 宫颈管直，易于插管，内部口 非常小并且本身是S形的。 提供信息 与项目目标相关，高剂量和低剂量宫内节育器被插入 通过子宫切除术对短尾猴和猪尾猕猴进行治疗。 我们的第一个研究 旨在测试抗孕激素宫内节育器是否可以抑制 孕酮对子宫内膜的影响。 低剂量和高剂量宫内节育器 放置宫内节育器后三天内诱发月经。 这 表明两者局部产生的抗孕激素量 高剂量和低剂量宫内节育器足以预防全身性 黄体酮维持子宫内膜在孕期的状态 状态。 对猴子进行治疗以诱导人工月经周期 并在一个周期结束时收集组织。 子宫内膜 暴露于空白宫内节育器与典型的宫内节育器没有显着差异 孕期子宫内膜，除了子宫内膜的量 组织比正常结束时的预期要少一些 循环。 抗孕激素宫内节育器导致子宫严重压缩 基质和 P 对腺体的影响的抑制 囊状动脉和螺旋动脉发育。 有证据表明 血管周围玻璃样变性与长期观察到的相似 术语全身性抗孕激素。 这些结果表明急性 通过宫内节育器给予局部抗孕激素可以抑制 子宫内膜发育，可能是系统性的替代方案 控制子宫内膜出血或作为基于子宫的治疗 避孕药。 资助 Lalor 基金会出版物 无