ANDROSTENEDIONE INCREASES ESTRADIOL LEVELS BUT NOT PRETERM LABOR

据报道，静脉注射给药 雄烯二酮(4A)通过增加 母体循环中雌二醇(E_2)浓度和 刺激夜间子宫活动增加(NAT Med 2：443， 1996年)。我们实验室的初步实验表明， E2-苯甲酸酯在非器质性流产中不会加速早产 动物(AJOG 145：920,1983)。因此，我们研究了4A的影响 在仪器化和非仪器化的恒河猴中给予SQ。 雄烯二酮(6-30 mg，bid，sq)给5只恒河猴服用 怀孕132-142天开始的猴子。有两只动物被 用母体和胎儿的血管和羊水进行检测 第122天的导尿管。三只动物没有做器皿和血液 是被静脉穿刺术抽出来的。一只胎盘动物早产 (第145天)治疗开始后60小时；所有其他动物 在21-40天后自然分娩(第160-172天) 治疗。早产的动物有夜间发作的症状 子宫活动度(UA) 4A给药，而另一只动物没有表现出夜间UA 直到分娩。没有一只之前出生的无器皿动物 学期。母体血浆激素水平如下所示(前= 治疗前；产后=产后；0=分娩天数；均值+扫描电子显微镜；* =不同于Pre，P&gt；0.05 ANOVA)E2E14A T DHTP4DHEAS前天数 皮质醇产程(pg/ml)(pg/ml)(ng/ml) (ng/ml)(ng/ml)前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后77q28 35q16 10.7q5.9 1.6q0.7 1.1q0.5 1.4q0.2 107q35 262q37这些数据表明 雄烯二酮给药后高水平的雌二醇不会 必然会导致早产。子宫功能不全 一些动物在手术器械后实现静止可能 与雄烯二酮相关的促进早产 行政管理。

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.