ACTH INFUSION INTO RHESUS MONKEY FETUS LEADS TO PREMATURE LABOR & DELIVERY

向恒河猴胎儿注入促肾上腺皮质激素会导致早产

• 批准号: 6116143
• 负责人: GEORGE J HALUSKA
• 金额: $ 9.03万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116143
• 关键词: Mammalia; clinical research; endocrine gland /system; health care; mother /infant health care; reproductive system; women's health

The activation of the hypothalamic-pituitary-adrenal axis in fetal sheep is the primary initiator of parturition; however, this same mechanism has not been proven to be important in primate parturition. To determine if adrenocorticotropic hormone (ACTH) can induce premature parturition in primates, we infused ACTH (0.1 U in 30 min, every 2 hrs; n=7) beginning on day 135 of pregnancy (term=167 days) until delivery occurred. A control group of animals (n=3) received saline vehicle infusions. All animals were surgically instrumented with fetal and maternal vascular and amniotic fluid catheters, fetal ECG and myometrial EMG electrodes. Uterine activity (UA) and fetal ECG were recorded continuously. The results of ACTH and vehicle infusion are listed in the following table (values are mean + SEM) * = P<0.05 (t-test) ACTH vs Vehicle Begin Infusion (day of preg) Onset Nocturnal UA (days) Days to Delivery Delivery (Day of Pregnancy) ACTH (n=6) 135.3 + 0.6 6.3 + 0.8 15.2 + 1.3 149.7 + 1.3 Vehicle (n=3) 135.7 + 1.8 24.7 + 2.7* 27.6 + 3.2* 163.3 + 1.5* One ACTH-treated animal was delivered by cesarean section at 165 days of pregnancy after prolonged labor and dystocia and was excluded from the data set. Mean (+ SEM) maternal and fetal steroid changes in ACTH-treated animals *=P<0.005 (Rank Sum Test) (n=6) Fetal Cortisol (ng/ml) Fetal DHEA-Sulfate (?g/ml) Fetal Androstene-dione (ng/ml) Fetal Estrone (pg/ml) Maternal Estradiol (pg/ml) Baseline 79 + 11 0.4 + .08 0.8 + 0.2 97 + 27 360 + 45 Labor 276 + 48* 6.6 + 3.1* 7.4 + 1.7* 519 + 170* 877 + 187* We conclude that infusion of ACTH into the fetal circulation activates fetal adrenal steroid biosynthesis causing increased secretion of glucocorticoids and androgens leading to increased estrogen and cortisol production and pre-term delivery in rhesus monkeys. FUNDING NIH HD06159, HD18185 PUBLICATIONS None

胎儿下丘脑-垂体-肾上腺轴的激活 羊是分娩的主要发起者；然而，这同样 尚未证明该机制在灵长类动物分娩中很重要。 确定促肾上腺皮质激素 (ACTH) 是否可以诱导 灵长类动物早产，我们注射 ACTH（30 分钟内 0.1 U， 每 2 小时一次； n=7) 从怀孕第 135 天开始（足月=167 天） 直到交货发生。 对照组动物 (n=3) 接受 盐水载体输注。 所有动物都经过外科手术 带有胎儿和母体血管和羊水导管，胎儿 心电图和肌层肌电图电极。 子宫活动 (UA) 和胎儿 连续记录心电图。 ACTH 和车辆的结果 输液列于下表中（数值为平均值 + SEM）* = P<0.05（t 检验）ACTH 与媒介物开始输注（怀孕当天）开始 夜间 UA（天） 分娩天数 分娩（怀孕当天） ACTH (n=6) 135.3 + 0.6 6.3 + 0.8 15.2 + 1.3 149.7 + 1.3 车辆 (n=3) 135.7 + 1.8 24.7 + 2.7* 27.6 + 3.2* 163.3 + 1.5* 一只 ACTH 治疗的动物 怀孕165天经剖腹产分娩 分娩和难产并被排除在数据集中。 平均值 (+ SEM) ACTH 治疗动物的母体和胎儿类固醇变化 *=P<0.005 （秩和检验）(n=6) 胎儿皮质醇 (ng/ml) 胎儿 DHEA 硫酸盐 (?g/ml) 胎儿雄烯二酮 (ng/ml) 胎儿雌酮 (pg/ml) 母体 雌二醇 (pg/ml) 基线 79 + 11 0.4 + .08 0.8 + 0.2 97 + 27 360 + 45 劳工 276 + 48* 6.6 + 3.1* 7.4 + 1.7* 519 + 170* 877 + 187* 我们 结论是，将 ACTH 输注到胎儿循环中会激活 胎儿肾上腺类固醇生物合成导致分泌增加 糖皮质激素和雄激素导致雌激素增加 恒河猴皮质醇的产生和早产。 资金 NIH HD06159、HD18185 出版物 无