Takeyoshi Masahiro, Sawaki Masakuni, Noda Shuji, Muroi Takako, Yamasaki Kanji
Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822 Ishii-machi, Hita-shi, Oita 8770061, Japan.
Reprod Toxicol. 2002 Jul-Aug;16(4):367-9. doi: 10.1016/s0890-6238(02)00043-6.
The immature rat uterotrophic assay has been proposed as a screening test method for detecting estrogenic and antiestrogenic chemicals. Although the immature rat uterotrophic assay is advantageous because the test animals are not traumatized by the ovariectomizing process, the effect of endogenous estrogen on ovarian and uterine weight in the immature animals that are used in immature rat uterotrophic assay has not received much attention. In this study, 19-day-old rats were treated with antide, a gonadotropin-releasing hormone antagonist, antide, to block gonadal production of endogenous estrogen. Uterine and ovarian weights of the antide-treated animals were markedly lower than those of control animals. This finding suggests that endogenous gonadal estrogen may already be acting on the uterus and ovaries in immature rats. Blocking endogenous estrogen with a gonadotropin-releasing hormone antagonist may enhance the sensitivity of the immature rat uterotrophic assay; however, the possibility that this protocol may interfere with the ability of the immature rat uterotrophic assay to detect centrally-mediated effects can not be discounted.
未成熟大鼠子宫增重试验已被提议作为一种检测雌激素和抗雌激素化学物质的筛选测试方法。尽管未成熟大鼠子宫增重试验具有优势,因为试验动物不会因去卵巢手术而受到创伤,但在未成熟大鼠子宫增重试验中使用的未成熟动物体内,内源性雌激素对卵巢和子宫重量的影响尚未得到足够关注。在本研究中,对19日龄大鼠使用促性腺激素释放激素拮抗剂安替肽进行处理,以阻断内源性雌激素的性腺分泌。经安替肽处理的动物的子宫和卵巢重量明显低于对照动物。这一发现表明,内源性性腺雌激素可能已经在未成熟大鼠的子宫和卵巢中发挥作用。用促性腺激素释放激素拮抗剂阻断内源性雌激素可能会提高未成熟大鼠子宫增重试验的灵敏度;然而,该方案可能干扰未成熟大鼠子宫增重试验检测中枢介导效应能力的可能性也不能被忽视。