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: 6453699
• 负责人: GEORGE J HALUSKA
• 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/6453699
• 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人;然而，这同样 机制尚未被证明是重要的灵长类动物分娩。 为了确定促肾上腺皮质激素（ACTH）是否可以诱导 在灵长类动物的早产中，我们输注ACTH（30分钟内0.1U， 每2小时一次; n=7），从妊娠第135天开始（足月=167天） 直到分娩发生。 对照组动物（n=3）接受 盐水载体输注。 所有动物均通过手术器械固定 胎儿和母体血管和羊水导管，胎儿 ECG和子宫肌层EMG电极。 子宫活动（UA）和胎儿 连续记录心电图。 ACTH和溶媒的结果 输注的平均值列于下表中（值为平均值± SEM）* = P<0.05（t检验）ACTH vs溶媒开始输注（妊娠当天） 夜间UA（天）分娩天数分娩（妊娠日）ACTH （n=6）135.3 + 0.6 6.3 + 0.8 15.2 + 1.3 149.7 + 1.3溶剂（n=3）135.7 + 1.8 24.7 + 2.7* 27.6 + 3.2* 163.3 + 1.5* 1只ACTH治疗动物 在妊娠165天后通过剖宫产分娩 分娩和难产，并从数据集中排除。 平均值（+ SEM） ACTH处理动物中母体和胎儿类固醇变化 *=P<0.005 (Rank总和检验）（n=6）胎仔皮质醇（ng/ml）胎仔硫酸脱氢表雄酮 (?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人工276 + 48* 6.6 + 3.1* 7.4 + 1.7* 519 + 170* 877 + 187* 我们 结论是ACTH注入胎儿循环激活 胎儿肾上腺类固醇的生物合成， 糖皮质激素和雄激素导致雌激素增加， 皮质醇的产生和早产的恒河猴。 资金 NIH HD 06159，HD 18185出版物无