ANDROSTENEDIONE INCREASES ESTRADIOL LEVELS BUT NOT PRETERM LABOR

雄烯二酮会增加雌二醇水平，但不会增加早产

• 批准号: 6247230
• 负责人: MILES J. NOVY
• 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/6247230
• 关键词: Mammalia; Primates; biological products; endocrine gland /system; hormones; mother /infant health care; reproductive system; women's health

It has been reported that intravenous administration of androstenedione ( 4A) leads to labor and delivery by increasing the concentration of estradiol (E2) in the maternal circulation and stimulating increased nocturnal uterine activity (Nat Med 2:443, 1996). Initial experiments in our laboratory demonstrated that E2-benzoate did not precipitate preterm delivery in non-instrumented animals (AJOG 145:920, 1983). We therefore studied the effect of 4A given SQ in instrumented and non-instrumented rhesus monkeys. Androstenedione was administered (6-30 mg, BID, SQ) to 5 rhesus monkeys beginning on day 132-142 of pregnancy. Two animals were instrumented with maternal and fetal vascular and amniotic fluid catheters on day 122. Three animals were not instrumented and blood was drawn by venipuncture. One instrumented animal delivered preterm (day 145) 60 hours after the beginning of treatment; all other animals delivered spontaneously at term (day 160-172) after 21-40 days of treatment. The animal that delivered early had nocturnal episodes of uterine activity (UA) prior to 4A administration whereas the other animal did not show nocturnal UA until delivery. None of the uninstrumented animals delivered before term. Maternal plasma hormone levels are shown below (Pre = pre-treatment; post = post-partum; 0 = day of delivery; mean + SEM; * = different from pre, P>0.05 ANOVA) Days Pre- E2 E1 4A T DHT P4 DHEAS Cortisol partum (pg/ml) (pg/ml) (ng/ml) (ng/ml) (ng/ml) (ng/ml) (ng/ml) (ng/ml) Pre 451q39 117q17 1.4q0.2 0.2q0.04 0.2q0.03 3.7q1.0 269q55 310q57 16-25 1960q129* 1073q158* 25.8q3.8* 4.4q0.3* 2.5q0.4* 3.5q0.5 154q16 334q33 6-15 1971q105* 1161q101* 52.2q17.6* 5.3q0.7* 3.01q0.5* 4.0q0.5 143q15 323q28 1-5 1553q173* 1178q317* 30.5q9.8* 4.1q0.9* 2.0q0.6* 3.6q0.5 187q33 321q39 0 1717q224* 1069q283 66.9q19.4* 6.5q1.4* 2.6q0.9* 5.9q2.6 174q18 356q75 Post 77q28 35q16 10.7q5.9 1.6q0.7 1.1q0.5 1.4q0.2 107q35 262q37 These data suggest that high levels of estradiol after androstenedione administration do not necessarily lead to preterm delivery. The inability of the uterus of some animals to achieve quiescence after surgical instrumentation may facilitate preterm delivery associated with androstenedione administration.

据报道，静脉给药 雄烯二酮（4A）通过增加 母体循环中雌二醇（E2）的浓度， 刺激增加的夜间子宫活动（NatMed 2：443， 1996年）。 我们实验室的初步实验表明， E2-苯甲酸酯在非器械妊娠中未引起早产。 动物（AJOG 145：920，1983）。 因此，我们研究了4A的效果。 在装有仪器和未装有仪器的恒河猴中给予SQ。 雄烯二酮给药（6-30 mg，BID，SQ）给5只恒河猴 从妊娠第132-142天开始。 两只动物 用母体和胎儿的血管和羊水 第122天的导管。 3只动物未使用仪器，血液 是通过静脉穿刺抽取的 1只植入器械的动物早产 (day 145）给药开始后60小时;所有其他动物 在分娩后21-40天（第160-172天）自然分娩 治疗 早期分娩的动物在夜间发作， 子宫活动（UA） 4A给药，而另一只动物未显示夜间UA 直到分娩 之前没有任何未使用器械的动物分娩 term. 母体血浆激素水平如下所示（Pre = 治疗前; post =产后; 0 =分娩日;平均值+ SEM; * =与治疗前不同，P>0.05 ANOVA）治疗前天数- E2 E1 4A T DHT P4 DHEAS 分娩皮质醇（pg/ml）（pg/ml）（ng/ml）（ng/ml）（ng/ml）（ng/ml） (ng/ml）（ng/ml）前体451 q39 117 q17 1.4q0.2 0.2q0.04 0.2q0.03 3.7q1.0 269q55 310q57 16-25 1960q129* 1073q158* 25.8q3.8* 4.4q0.3* 2.5q0.4* 3.5q0.5 154q16 334q33 6-15 1971q105* 1161q101* 52.2q17.6* 5.3q0.7* 3.01q0.5* 4.0q0.5 143q1 - 5 323q28 1-5 1553q173* 1178q317* 30.5q9.8* 4.1q0.9* 2.0q0.6* 3.6q0.5 187q33 321q39 0 1717q224* 1069q283 66.9q19.4* 6.5q1.4* 2.6q0.9* 5.9q2.6 174 q18 356 q75岗位77 q28 35 q16 10.7q5.9 1.6q0.7 1.1q0.5 1.4q0.2 107 q35 262 q37这些数据表明， 雄烯二酮给药后高水平的雌二醇不 必然导致早产。 子宫的无能 一些动物在手术器械后达到安静， 促进雄烯二酮相关早产 局