Poulet F M, Roessler M L, Vancutsem P M
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana 61802, USA.
Reprod Toxicol. 1997 Nov-Dec;11(6):815-22. doi: 10.1016/s0890-6238(97)00065-8.
Neonatal treatment of rodents with the widely used antiestrogen tamoxifen causes endometrial cancer and reproductive tract lesions reminiscent of the diethylstilbestrol (DES) syndrome. To evaluate the initial alterations induced in the developing uterus by tamoxifen or DES, neonatal Sprague-Dawley rat pups received 100 micrograms of tamoxifen (Group 1), 1 microgram of DES (Group 2), or vehicle (Group 3) subcutaneously on days 1 through 5, and their uteri were studied by light microscopy, 5-bromo-2' deoxyuridine immunohistochemistry, and computer-based morphometry. At Postnatal Day 6, epithelial hypertrophy (184.3% and 237.9% of controls) and myometrial thickening (151.9% and 180.0%) accounted for the uterotrophic effects of tamoxifen and DES. Evidence of secretory activity in epithelial cells, reduction of the epithelial BrdU-labeling index to 18.1% (tamoxifen) and 41.1% (DES) of controls, premature endometrial and myometrial differentiation, and the presence of eosinophils in both treatment groups suggested that tamoxifen exerted a DES-like estrogenic action on the developing uterus. These findings indicate that immediate epithelial and stromal-myometrial uterine alterations are found at Postnatal Day 6 after neonatal tamoxifen treatment.
用广泛使用的抗雌激素他莫昔芬对新生啮齿动物进行治疗会引发子宫内膜癌以及类似于己烯雌酚（DES）综合征的生殖道病变。为了评估他莫昔芬或DES对发育中的子宫所引发的初始改变，在出生后第1至5天，对新生的斯普拉格-道利大鼠幼崽皮下注射100微克他莫昔芬（第1组）、1微克DES（第2组）或赋形剂（第3组），并通过光学显微镜、5-溴-2'-脱氧尿苷免疫组织化学以及基于计算机的形态计量学对它们的子宫进行研究。在出生后第6天，上皮肥大（分别为对照组的184.3%和237.9%）和肌层增厚（分别为151.9%和180.0%）是他莫昔芬和DES产生子宫营养作用的表现。上皮细胞分泌活动的证据、上皮BrdU标记指数降至对照组的18.1%（他莫昔芬）和41.1%（DES）、子宫内膜和肌层过早分化以及两个治疗组中嗜酸性粒细胞的存在表明，他莫昔芬对发育中的子宫发挥了类似DES的雌激素作用。这些发现表明，在新生大鼠接受他莫昔芬治疗后的出生后第6天，即可发现子宫上皮和基质-肌层的即时改变。
