Althaus Z R, Bailey J R, Leakey J E, Slikker W
Dev Pharmacol Ther. 1986;9(5):332-49. doi: 10.1159/000457112.
The synthetic glucocorticoid dexamethasone (DEX) and endogenous cortisol were compared in 2 groups of pregnant monkeys of gestational age 143-148 days. In group I, a fetal intraplacental vein and a maternal femoral vessel were catheterized. 3H-Cortisol and 14C-DEX were administered intravenously along with 0.2 mg/kg unlabelled DEX to the mother. Blood and tissue samples were collected to 3 h and urine and feces to 96 h. In group II, 4 of the 7 animals were predosed with DEX 10 mg/kg s.c. for 3 days prior to surgery. The fetus was removed by cesarean section and the in situ placenta was perfused via the umbilical arteries at 15 ml/min X 8 min with 3H-cortisol/14C-DEX in Hanks' balanced salt solution. Samples were taken from the umbilical vein and uterine vein. In group I, HPLC analysis of paired maternal and fetal plasma samples taken at 10, 20, 60, 120 and 180 min after dosing indicated that the F/M DEX ratio was significantly greater than the F/M cortisol ratio. In fetal lung and liver tissues analyzed, less than 2% of the cortisol remained unmetabolized by 3 h, whereas greater than or equal to 76% DEX remained as parent compound. There was no significant difference between the percentage of DEX (83 +/- 7%) and cortisol (73 +/- 3%) recovery in maternal urine and feces. In group II, HPLC analysis of paired umbilical vein and uterine vein samples at 2, 4 and 8 min showed that by 8 min 24% of cortisol was converted to cortisone by the uteroplacenta, but only 2.5% of DEX was converted to a metabolite. In DEX-pretreated animals both uterine vein and umbilical vein samples indicated an increase in cortisol to cortisone conversion. A significant increase in DEX metabolism was evident in the uterine vein samples but not the umbilical vein. These data indicate that the fetus is exposed to a higher proportion of DEX than cortisol and that the uteroplacenta plays a larger role in cortisol than in DEX metabolism. In addition, these data suggest that DEX pretreatment enhances the ability of the uteroplacenta to convert cortisol to cortisone.
在两组孕龄为143 - 148天的怀孕猴子中，对合成糖皮质激素地塞米松（DEX）和内源性皮质醇进行了比较。在第一组中，将胎儿的胎盘内静脉和母体的股血管进行插管。将3H - 皮质醇和14C - DEX与0.2mg/kg未标记的DEX一起静脉注射给母体。采集血液和组织样本至3小时，尿液和粪便样本至96小时。在第二组中，7只动物中有4只在手术前3天皮下注射10mg/kg的DEX进行预给药。通过剖宫产取出胎儿，并通过脐动脉以15ml/min×8min的速度用含3H - 皮质醇/14C - DEX的汉克斯平衡盐溶液灌注原位胎盘。从脐静脉和子宫静脉采集样本。在第一组中，给药后10、20、60、120和180分钟采集的配对母体和胎儿血浆样本的HPLC分析表明，胎儿/母体DEX比值显著大于胎儿/母体皮质醇比值。在分析的胎儿肺和肝组织中，到3小时时，不到2%的皮质醇未被代谢，而大于或等于76%的DEX仍为母体化合物。母体尿液和粪便中DEX（83±7%）和皮质醇（73±3%）的回收率没有显著差异。在第二组中，对脐静脉和子宫静脉样本在2、4和8分钟时进行的HPLC分析表明，到8分钟时，24%的皮质醇被子宫胎盘转化为可的松，但只有2.5%的DEX转化为代谢物。在DEX预处理的动物中，子宫静脉和脐静脉样本均表明皮质醇向可的松的转化增加。子宫静脉样本中DEX代谢有显著增加，但脐静脉中没有。这些数据表明，胎儿接触DEX的比例高于皮质醇，并且子宫胎盘在皮质醇代谢中比在DEX代谢中起更大的作用。此外，这些数据表明DEX预处理增强了子宫胎盘将皮质醇转化为可的松的能力。
