Lamartiniere C A
Endocrinology. 1979 Oct;105(4):1031-5. doi: 10.1210/endo-105-4-1031.
Hepatic histidase was used as an enzyme marker for the study of neonatal programming in intact rats. Diethylstilbestrol (DES) or 17 beta-estradiol (E2) treatment for days, 2, 4, and 6 post partum resulted in decreased histidase activities in the adult female, but no effect was seen in prepubertal male and female rats or in adult males. In contrast, similar neonatal doses of testosterone propionate (TP) had no effect on histidase. Dose-response experiments demonstrate a 3-fold greater neonatal sensitivity to DES than to E2. The action of neonatal estrogen treatment is demonstrated to be permanent and irreversible. Neonatal treatment with E2, DES, or TP resulted in decreased uterine wet weights in adult females (E2 less than DES less than TP less than controls). Circulating sera estrogen levels were lower in adult E2- and DES-treated females than in TP-treated and control females. Our results suggest that these alterations may be due to direct toxic effects on the postnatal development of the female reproductive tract and endocrine system and/or to organizational effects on nerve endings in the hypothalamus that result in programming for altered sexual differentiation of hepatic metabolism.
肝组织氨酸酶被用作研究完整大鼠新生儿编程的酶标志物。产后第2、4和6天用己烯雌酚（DES）或17β-雌二醇（E2）处理，导致成年雌性大鼠的组织氨酸酶活性降低，但青春期前雄性和雌性大鼠或成年雄性大鼠未见影响。相比之下，类似的新生儿剂量丙酸睾酮（TP）对组织氨酸酶没有影响。剂量反应实验表明，新生儿对DES的敏感性比对E2高3倍。新生儿雌激素处理的作用被证明是永久性和不可逆的。用E2、DES或TP进行新生儿处理导致成年雌性大鼠子宫湿重降低（E2＜DES＜TP＜对照组）。成年E2和DES处理的雌性大鼠循环血清雌激素水平低于TP处理和对照雌性大鼠。我们的结果表明，这些改变可能是由于对雌性生殖道和内分泌系统产后发育的直接毒性作用和/或对下丘脑神经末梢的组织学作用，导致肝脏代谢性分化改变的编程。
