Ankley Gerald T, Jensen Kathleen M, Makynen Elizabeth A, Kahl Michael D, Korte Joseph J, Hornung Michael W, Henry Tala R, Denny Jeffrey S, Leino Richard L, Wilson Vickie S, Cardon Mary C, Hartig Phillip C, Gray L Earl
U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota 55804, USA.
Environ Toxicol Chem. 2003 Jun;22(6):1350-60.
Trenbolone acetate is a synthetic steroid that is extensively used in the United States as a growth promoter in beef cattle. The acetate is administered to livestock via slow-release implants; some is converted by the animal to 17-beta-trenbolone, a relatively potent androgen receptor agonist in mammalian systems. Recent studies indicate that excreted 17-beta-trenbolone is comparatively stable in animal waste, suggesting the potential for exposure to aquatic animals via direct discharge, runoff, or both. However, little is known concerning the toxicity of trenbolone to fish. Our goal was to assess the effects of 17-beta-trenbolone on reproductive endocrinology of the fathead minnow (Pimephales promelas). An in vitro competitive binding study with the fathead minnow androgen receptor demonstrated that 17-beta-trenbolone had a higher affinity for the receptor than that of the endogenous ligand, testosterone. Male and female fish were exposed for 21 d to nominal (target) concentrations of 17-beta-trenbolone ranging from 0.005 to 50 microg/L. Fecundity of the fish was significantly reduced by exposure to measured test concentrations > or = 0.027 microg/ L. The 17-beta-trenbolone was clearly androgenic in vivo at these concentrations, as evidenced by the de novo production in females of dorsal (nuptial) tubercles, structures normally present only on the heads of mature males. Plasma steroid (testosterone and beta-estradiol) and vitellogenin concentrations in the females all were significantly reduced by exposure to 17-beta-trenbolone. The 17-beta-trenbolone also altered reproductive physiology of male fathead minnows, albeit at concentrations much higher than those producing effects in females. Males exposed to 17-beta-trenbolone at 41 microg/L (measured) exhibited decreased plasma concentrations of 11-ketotestosterone and increased concentrations of beta-estradiol and vitellogenin. Overall, our studies indicate that 17-beta-trenbolone is a potent androgen and reproductive toxicant in fish. Given the widespread use of trenbolone acetate as a growth promoter, and relative stability of its metabolites in animal wastes, further studies are warranted to assess potential ecological risk.
醋酸群勃龙是一种合成类固醇,在美国被广泛用作肉牛的生长促进剂。醋酸群勃龙通过缓释植入物施用于牲畜;其中一些会被动物转化为17-β-群勃龙,这是一种在哺乳动物系统中相对强效的雄激素受体激动剂。最近的研究表明,排泄出的17-β-群勃龙在动物粪便中相对稳定,这表明其有可能通过直接排放、径流或两者兼而有之的方式暴露于水生动物。然而,关于群勃龙对鱼类的毒性知之甚少。我们的目标是评估17-β-群勃龙对黑头呆鱼(Pimephales promelas)生殖内分泌学的影响。一项针对黑头呆鱼雄激素受体的体外竞争性结合研究表明,17-β-群勃龙对该受体的亲和力高于内源性配体睾酮。将雄性和雌性鱼类暴露于浓度范围为0.005至50微克/升的标称(目标)浓度的17-β-群勃龙中21天。当暴露于测量的测试浓度≥0.027微克/升时,鱼类的繁殖力显著降低。在这些浓度下,17-β-群勃龙在体内明显具有雄激素活性,雌性背部(婚姻)瘤的重新产生证明了这一点,这种结构通常只出现在成熟雄性的头部。雌性血浆类固醇(睾酮和β-雌二醇)和卵黄蛋白原浓度在暴露于17-β-群勃龙后均显著降低。17-β-群勃龙也改变了雄性黑头呆鱼的生殖生理,尽管其浓度远高于对雌性产生影响的浓度。暴露于41微克/升(测量值)的17-β-群勃龙的雄性,其血浆11-酮睾酮浓度降低,β-雌二醇和卵黄蛋白原浓度升高。总体而言,我们的研究表明,17-β-群勃龙是鱼类中的一种强效雄激素和生殖毒物。鉴于醋酸群勃龙作为生长促进剂的广泛使用及其代谢物在动物粪便中的相对稳定性,有必要进一步研究以评估潜在的生态风险。