ANTI PROGESTIN CHRONIC LOW DOSE DEPENDENT ENDOMETRIAL ATROPHY: MONKEY

抗孕激素慢性低剂量依赖性子宫内膜萎缩：猴

• 批准号: 6247240
• 负责人: STOUFFER RICHARD L
• 金额: $ 4.86万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247240
• 关键词: Mammalia; Primates; hormones; reproductive system; women's health

Antiprogestins are reported to inhibit endometrial maturation in cycling macaques and women. In this study, we investigated the long-term effects of low dose treatment with the new antiprogestin ZK 137 316 on endometrial morphology in intact, naturally cycling rhesus monkeys. Four groups of monkeys were injected daily for 5 cycles with 3 doses of ZK 137 316 (none (vehicle), 0.01, 0.03 and 0.1 mg /kg body weight, i.m.). Oviducts and uteri (n=3/ group) were collected on day 22 of the 5th cycle in the vehicle, 0.01 and 0.03 mg/kg groups, or 6-7 days after the estradiol peak in the 0.1 mg/kg group. Oviduct and uterine tissues were weighed and samples were fixed, embedded in glycolmethacrylate and sectioned for histology. Mean endometrial weight (qSE) from vehicle, 0.01, 0.03 and 0.1 mg kg groups were 510 q 10, 196 q 111, 36 q 3 and 43 q 13 mg, respectively (P<0.05). The endometrium from vehicle-treated monkeys was fully differentiated with large secretory glands and well-developed spiral arteries. The endometrium of all ZK 137 316 treated animals showed glandular atrophy, stromal compaction, artery degradation and venous dilation, and in the 0.1 mg/kg group, almost complete loss of endometrial glands and spiral arteries. These data indicate that ZK 137 316 can profoundly suppress endometrial development in a dose-dependent manner in naturally cycling rhesus monkeys with normal levels of estrogen. There were no significant effects of ZK 137 316 on myometrial or oviductal weights compared to vehicle treated controls. In summary, chronic treatment with low dose ZK 137 316 produced a dramatic "antiproliferative" effect in the rhesus endometrium without signs of unopposed estrogen action in the uterus. Because such atrophied endometria are unlikely to support implantation, our laboratory is now evaluating the contraceptive efficacy of chronic low dose ZK 137 316 treatment in rhesus monkeys.

据报道，抗孕激素抑制子宫内膜成熟， 骑自行车的猕猴和女人 在这项研究中，我们调查了 低剂量新抗白细胞介素ZK治疗的长期效果 137 316对完整、自然周期恒河猴子宫内膜形态的影响 猴子 四组猴子每天注射5个周期， ZK 137 316 3次给药（无（溶剂）、0.01、0.03和0.1 mg /kg体重） 重量，i.m.）。在第1天采集输卵管和子宫（n=3/组） 溶剂、0.01和0.03 mg/kg组第5个周期的22例，或6-7例 0.1 mg/kg组雌二醇峰值后30天。 输卵管和 将子宫组织称重，并将样品固定，包埋在 乙二醇甲基丙烯酸酯并切片用于组织学。 平均子宫内膜 溶剂、0.01、0.03和0.1 mg/kg组的体重（qSE）为510 q 10、196 q111、36 q3和43 q13 mg（P<0.05）。 的 来自溶剂处理猴的子宫内膜完全分化， 分泌腺大，螺旋动脉发达。 的 所有ZK 137 316治疗组动物的子宫内膜均显示腺性 萎缩、基质致密化、动脉退化和静脉扩张， 在0.1 mg/kg组中，子宫内膜腺体几乎完全丧失 和螺旋动脉 这些数据表明，ZK 137 316可以 以剂量依赖性方式深刻抑制子宫内膜发育 在雌激素水平正常的自然循环恒河猴中。 ZK 137 316对子宫肌层或 与溶媒处理对照相比的输卵管重量。 总的来说， 用低剂量ZK 137 316进行慢性治疗， 在恒河猴子宫内膜中的“抗增殖”作用， 子宫内无对抗的雌激素作用。 因为这种萎缩 由于胚胎不太可能支持移植，我们的实验室现在 评价长期低剂量ZK 137 316的避孕效果 治疗恒河猴。