Bonner M J
Zoology Department, North Carolina State University, Raleigh.
J Clin Pharmacol. 1994 Jun;34(6):713-8. doi: 10.1002/j.1552-4604.1994.tb02029.x.
Exposure to phenobarbital in utero results in sex-dependent altered neonatal behavior and reproductive maturation in hamsters. Prenatal phenobarbital-exposed (40 mg/kg subcutaneous to pregnant dams) male pups have at least 30% less pivoting activity and ultrasonic calling (high-frequency sounds produced by pups when separated from the nest) when compared with control pups born to saline-injected dams. As prenatal phenobarbital-treated male and female hamsters mature, there is a dose-dependent (20, 40, and 60 mg/kg) 2- to 5-day delay, respectively, according to sex, in puberty onset. Both sexes exhibited 30% lighter than control's adrenal weights associated with prenatal phenobarbital exposure. Although gonadal weights for males exposed to phenobarbital in utero were not affected, females had up to 33% lighter ovarian weights when compared with controls. Females exposed to phenobarbital in utero also had approximately 40% more irregular estrous cycles. Gonadal hormones act by means of Central Releasing Factor on pituitary ACTH secretion. Additional treatment during the neonatal period with 10 IU ACTH decreased the percentage of irregular estrous cycles and shortened the delay in puberty onset to near-control values in prenatally phenobarbital-treated females.
子宫内暴露于苯巴比妥会导致仓鼠出现性别依赖性的新生行为改变和生殖成熟异常。与注射生理盐水的母鼠所生的对照幼崽相比，产前暴露于苯巴比妥（给怀孕母鼠皮下注射40毫克/千克）的雄性幼崽的旋转活动和超声叫声（幼崽与巢穴分离时发出的高频声音）至少减少30%。随着产前接受苯巴比妥治疗的雄性和雌性仓鼠的成熟，根据性别不同，青春期开始分别出现剂量依赖性（20、40和60毫克/千克）的2至5天延迟。与产前暴露于苯巴比妥相关，两性的肾上腺重量均比对照组轻30%。虽然子宫内暴露于苯巴比妥的雄性的性腺重量未受影响，但与对照组相比，雌性的卵巢重量轻多达33%。子宫内暴露于苯巴比妥的雌性的发情周期不规则情况也多出约40%。性腺激素通过中枢释放因子作用于垂体促肾上腺皮质激素的分泌。在新生期用10国际单位促肾上腺皮质激素进行额外治疗，可降低产前接受苯巴比妥治疗的雌性发情周期不规则的百分比，并将青春期开始的延迟缩短至接近对照组的值。
