Gupta C, Yaffe S J
Pediatr Res. 1981 Dec;15(12):1488-91. doi: 10.1203/00006450-198112000-00006.
Phenobarbital (PB) (40 mg/kg/day) was administered to pregnant rats at 12 to 20, 14 to 20, and 17 to 20 days of gestation and female offspring were tested for the onset of puberty, estrous cycle pattern, and fertility. Another group of rats received PB (20 mg/kg/day) during the neonatal period (1 to 8 days). PB administration during both the pre- and postnatal periods resulted in a significant delay in the onset of puberty (control: 34.6 +/- 1.2 days, PB: 37.5 +/- 1.2 days), disorders of estrous cycle (control: normal cycles 91%, PB: normal cycles 40%), and infertility (control: 100% fertile PB: 50% fertile). Associated with these effects, we observed high levels of estrogen in plasma (control: 58.5 +/- 12.2 pg/ml, PB: 155.2 +/- 25.1 pg/ml) and increased estrogen receptors in the uterus (control: 0.136 +/- 0.026 pmole/mg protein, PB: 0.242 +/- 0.031 pmole/mg protein. This study shows that PB administration only during the period of neuroendocrine differentiation (17 to 20 days of pregnancy and 1 to 8 postnatal days) is capable of producing all of the adverse effects of PB, indicating that its action is upon neuroendocrine development.
在妊娠第12至20天、14至20天和17至20天，给怀孕大鼠注射苯巴比妥（PB）（40毫克/千克/天），并对雌性后代进行青春期开始时间、发情周期模式和生育能力测试。另一组大鼠在新生儿期（出生后1至8天）接受PB（20毫克/千克/天）。产前和产后期间给予PB均导致青春期开始时间显著延迟（对照组：34.6±1.2天，PB组：37.5±1.2天）、发情周期紊乱（对照组：正常周期91%，PB组：正常周期40%）以及不育（对照组：100%可育，PB组：50%可育）。与这些影响相关，我们观察到血浆中雌激素水平升高（对照组：58.5±12.2皮克/毫升，PB组：155.2±25.1皮克/毫升）以及子宫中雌激素受体增加（对照组：0.136±0.026皮摩尔/毫克蛋白，PB组：0.242±0.031皮摩尔/毫克蛋白）。本研究表明，仅在神经内分泌分化期（妊娠第17至20天和出生后1至8天）给予PB就能产生PB的所有不良影响，表明其作用于神经内分泌发育。
