Kamiya K, Sato T, Nishimura N, Goto Y, Kano K, Iguchi T
Graduate School of Integrated Science, Yokohama City University, Japan.
Exp Clin Endocrinol Diabetes. 1996;104(2):111-22. doi: 10.1055/s-0029-1211432.
Perinatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. The dynamics of the induction of estrogen receptor (ER), c-jun, c-fos and c-myc mRNAs by 17 beta-estradiol (E2) was examined in the uterus and vagina of neonatally DES-exposed and -unexposed ovariectomized adult mice. In the uterus of neonatally DES-unexposed ovariectomized mice, the expression of ER mRNA increased within 1 h after E2 administration and declined by 12 h thereafter. ER mRNA in the vagina decreased within 1 h after the stimulation and recovered by 12 h thereafter. In the uterus, c-jun and c-fos mRNAs increased in concentration within 1 h after E2 administration, showing a peak 3 h after the stimulation; they decreased with time thereafter. In the vagina, the concentration of c-jun and c-fos mRNAs increased rapidly, reaching a peak within 1 h after the stimulation. However, the expression of c-myc in uterus and vagina was not changed by postpuberal E2. These results suggest that estrogen regulation of ER and proto-oncogene mRNAs in the vagina differs from those in the uterus. In the neonatally DES-exposed ovariectomized adult mice, uterine ER mRNA expression levels were significantly higher than in the unexposed ovariectomized controls; however, vaginal levels were drastically lower than in the controls. Expression of c-jun and c-fos mRNAs was greater in both the uterus (3- and 6-fold, respectively) and the vagina (18- and 4-fold) of neonatally DES-exposed mice than in controls. The ER mRNA and the increased levels of c-fos and c-jun mRNAs in both uterus and vagina of neonatally DES-exposed ovariectomized mice were not further altered by post-puberal E2 and may be related to ovary-independent persistent changes in the genital tract.
用包括己烯雌酚（DES）在内的天然和合成雌激素对雌性小鼠进行围产期治疗，会导致阴道上皮出现不依赖雌激素的持续增殖和角质化。在新生期暴露于DES和未暴露于DES的成年去卵巢小鼠的子宫和阴道中，研究了17β-雌二醇（E2）对雌激素受体（ER）、c-jun、c-fos和c-myc mRNA诱导的动力学。在新生期未暴露于DES的成年去卵巢小鼠的子宫中，E2给药后1小时内ER mRNA表达增加，此后12小时下降。阴道中的ER mRNA在刺激后1小时内下降，此后12小时恢复。在子宫中，E2给药后1小时内c-jun和c-fos mRNA浓度增加，刺激后3小时达到峰值；此后随时间下降。在阴道中，c-jun和c-fos mRNA浓度迅速增加，刺激后1小时内达到峰值。然而，青春期后E2对子宫和阴道中c-myc的表达没有影响。这些结果表明，雌激素对阴道中ER和原癌基因mRNA的调节与子宫不同。在新生期暴露于DES的成年去卵巢小鼠中，子宫ER mRNA表达水平显著高于未暴露的去卵巢对照；然而，阴道水平远低于对照。新生期暴露于DES的小鼠子宫（分别为3倍和6倍）和阴道（分别为18倍和4倍）中c-jun和c-fos mRNA的表达均高于对照。新生期暴露于DES的成年去卵巢小鼠子宫和阴道中的ER mRNA以及c-fos和c-jun mRNA的增加水平在青春期后E2作用下未进一步改变，可能与生殖道中不依赖卵巢的持续变化有关。
