Agrawal A K, Pampori N A, Shapiro B H
Laboratories of Biochemistry, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6048.
Am J Physiol. 1995 Mar;268(3 Pt 1):E439-45. doi: 10.1152/ajpendo.1995.268.3.E439.
Growth hormone was secreted in sexually dimorphic patterns in both 65- and 150-day-old rats (i.e., "on-off" pulsatile for males and "continuous" pulsatile for females), but as a result of a 200-400% increase in pulse levels the mean concentration of hormone in the circulation was about two times as great in the younger animals. Neonatal exposure to phenobarbital at anticonvulsant therapeutic doses for the rat reduced the pulse amplitudes of circulating growth hormone in both the 65- and 150-day-old males but only in the 65-day-old females. As expected, neonatal administration of the barbiturate produced an almost immediate increase in the activities of the hepatic monooxygenases, as measured by hexobarbital metabolism, which declined to noninduction levels after treatment ceased. Contrary to the well-known transient effects of phenobarbital, at around the time of sexual maturity when gender-dependent differences in hepatic monooxygenases appear (males > females), we observed a second "round" of enzyme induction that persisted in both sexes for the remainder of the study (180 days). Because growth hormone is the primary regulator of sex-dependent hepatic monooxygenases, we have proposed that the abnormal plasma growth hormone profiles produced by neonatal phenobarbital are responsible for the permanent induction of hepatic monooxygenases.
生长激素在65日龄和150日龄大鼠中均以性别二态性模式分泌（即，雄性为“开-关”脉冲式，雌性为“连续”脉冲式），但由于脉冲水平增加200%-400%，幼龄动物循环中激素的平均浓度约为原来的两倍。新生大鼠以抗惊厥治疗剂量暴露于苯巴比妥，会降低65日龄和150日龄雄性大鼠以及仅65日龄雌性大鼠循环生长激素的脉冲幅度。正如预期的那样，通过己巴比妥代谢测定，新生大鼠给予巴比妥酸盐后肝单加氧酶的活性几乎立即增加，治疗停止后活性降至非诱导水平。与苯巴比妥众所周知的短暂效应相反，在性成熟前后，当肝单加氧酶出现性别依赖性差异时（雄性>雌性），我们观察到第二轮酶诱导，在研究的剩余时间（180天）内，两性中这种诱导持续存在。由于生长激素是性别依赖性肝单加氧酶的主要调节因子，我们提出新生期苯巴比妥产生的异常血浆生长激素谱是肝单加氧酶永久诱导的原因。
