Kang Hwan Goo, Jeong Sang Hee, Cho Joon Hyoung, Kim Dong Gyu, Park Jong Myung, Cho Myung Haing
National Veterinary Research and Quarantine Service, Division of Toxicology, 480, Anyang 6-dong, Anyang city 430-824, Republic of Korea.
Toxicology. 2004 Jul 1;199(2-3):219-30. doi: 10.1016/j.tox.2004.02.025.
Chlorpyrifos-methyl (CPM), an organophosphate insecticide, widely used for grain storage and agriculture, has been suspected as endocrine disrupter by a few in vitro studies. This study was performed to investigate the (anti-) estrogenicity and (anti-) androgenicity of CPM in vivo using immature rat uterotrophic assay and rat Hershberger assay. CPM with or without 17beta-estradiol were administered to 20 days old female rats to investigate its (anti-) estrogenic activity. Uterine and vaginal weight, uterine epithelial cell height were not affected by the treatment of CPM (2, 10, 50, 250 mg/kg). CPM 250 mg/kg potentiated relative vagina weight in 17beta-estradiol treated immature female rats without any changing of uterine weight. Relative liver weight was increased with decrease of body weight by CPM 250 mg/kg treatment. Uterine cell proliferation tested with bromodeoxyuridine labeling index was not observed in CPM treated rats. CPM with or without testosterone propionate were administered to castrated rat of 51 days old for 10 days to investigate the (anti-)androgenic activity,. The weight of relative and absolute androgen-dependent accessory sex organs; seminal vesicle with coagulating glands (SV/CG), ventral prostate gland (VP), glans penis (GP), levator ani plus bulbocarvernosus muscle (LABC) and Cowper's gland (CG,) were unchanged by the treatment of CPM alone. While CPM induced the increase of relative adrenal gland weight, CPM 50mg/kg decreased the weights of CV/CG, VP, CG and LABC without change of GP without changing of GP when it was treated with TP. In conclusion, CPM dose not show estrogenic and anti-estrogenic activity in immature female rats, but it represents anti-androgenic activity by inhibition of the TP-stimulated increase of the weight of accessory sex organs.
甲基毒死蜱(CPM)是一种有机磷杀虫剂,广泛用于谷物储存和农业领域,一些体外研究怀疑它是内分泌干扰物。本研究旨在通过未成熟大鼠子宫增重试验和大鼠赫什伯格试验,在体内研究CPM的(抗)雌激素活性和(抗)雄激素活性。将含或不含17β-雌二醇的CPM给予20日龄雌性大鼠,以研究其(抗)雌激素活性。CPM(2、10、50、250mg/kg)处理对子宫和阴道重量、子宫上皮细胞高度无影响。250mg/kg的CPM增强了17β-雌二醇处理的未成熟雌性大鼠的相对阴道重量,而子宫重量未发生任何变化。250mg/kg的CPM处理使相对肝脏重量增加,同时体重下降。在CPM处理的大鼠中,未观察到用溴脱氧尿苷标记指数检测的子宫细胞增殖。将含或不含丙酸睾酮的CPM给予51日龄去势大鼠10天,以研究其(抗)雄激素活性。单独使用CPM处理对相对和绝对雄激素依赖性附属生殖器官的重量没有影响,这些器官包括精囊与凝固腺(SV/CG)、腹侧前列腺(VP)、阴茎头(GP)、提肛肌加球海绵体肌(LABC)和尿道球腺(CG)。虽然CPM导致相对肾上腺重量增加,但50mg/kg的CPM在与丙酸睾酮共同处理时,使CV/CG、VP、CG和LABC的重量降低,而GP的重量未改变。总之,CPM在未成熟雌性大鼠中未表现出雌激素和抗雌激素活性,但通过抑制丙酸睾酮刺激的附属生殖器官重量增加,表现出抗雄激素活性。