Sone Kiyoaki, Hinago Megumi, Itamoto Misaki, Katsu Yoshinao, Watanabe Hajime, Urushitani Hiroshi, Tooi Osamu, Guillette Louis J, Iguchi Taisen
Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan.
Gen Comp Endocrinol. 2005 Sep 1;143(2):151-60. doi: 10.1016/j.ygcen.2005.03.007. Epub 2005 Apr 13.
Endocrine disrupting chemicals can affect normal hormone dependent processes through numerous mechanisms, including ligand mimicky. 17beta-Trenbolone (TB), a pharmaceutical, androgenic, anabolic steroid, is a potent agonist of androgen receptors, and has been extensively used as a growth promoter for beef cattle in the US. The effects of TB on adult and newborn mosquitofish (Gambusia affinis affinis) were examined. Two forms of mosquitofish androgen receptor (AR), ARalpha and ARbeta, were cloned. The mRNA expression levels of ARalpha and ARbeta were transiently increased in the anal fin of adult females at day 3 following exposure to TB (1-10 microg/L) or methyltestosterone (MT) (0.1-10 microg/L), a pharmaceutical androgen used as a positive control. Gonopodium differentiation from the adult female anal fin was induced after 28 days of exposure to TB (1-10 microg/L) or MT (0.1-10 microg/L). Gonopodium differentiation also was induced in all mosquitofish fry exposed for 28 days to 0.3, 1 or 10 microg/L TB. Furthermore, spermatozoa were observed histologically in the testes of male fry exposed for 28 days to 1 or 10 microg/L TB; spermatozoa are normally observed only in the testes of mature males. Surprisingly, all female fry exposed for 28 days to 1 or 10 microg/L TB displayed the formation of an ovotestis, as spermatozoa were found in the ovary. Thus, TB, like MT, induced masculinization of the anal fin accompanied by a transient up-regulation of ARalpha and ARbeta in adult females. TB also induced differentiation of the anal fin into a gonopodium in fry of both sexes, stimulated precocious spermatogenesis in the testes of males and the formation of ovotestes in females.
内分泌干扰化学物质可通过多种机制影响正常的激素依赖过程,包括配体模拟。17β - 群勃龙(TB)是一种药用的雄激素、合成代谢类固醇,是雄激素受体的强效激动剂,在美国已被广泛用作肉牛的生长促进剂。研究了TB对成年和新生食蚊鱼(盖氏食蚊鱼)的影响。克隆了食蚊鱼雄激素受体(AR)的两种形式,即ARα和ARβ。在成年雌性食蚊鱼暴露于TB(1 - 10微克/升)或甲基睾酮(MT)(0.1 - 10微克/升,一种用作阳性对照的药用雄激素)3天后,其臀鳍中ARα和ARβ的mRNA表达水平短暂升高。在暴露于TB(1 - 10微克/升)或MT(0.1 - 10微克/升)28天后,成年雌性食蚊鱼的臀鳍诱导分化为生殖足。在所有暴露于0.3、1或10微克/升TB 28天的食蚊鱼苗中,臀鳍也诱导分化为生殖足。此外,在暴露于1或10微克/升TB 28天的雄性鱼苗的睾丸中,通过组织学观察到了精子;精子通常只在成熟雄性的睾丸中观察到。令人惊讶的是,所有暴露于1或10微克/升TB 28天的雌性鱼苗都显示出卵睾的形成,因为在卵巢中发现了精子。因此,TB与MT一样,诱导成年雌性食蚊鱼臀鳍雄性化,并伴有ARα和ARβ的短暂上调。TB还诱导两性鱼苗的臀鳍分化为生殖足,刺激雄性鱼苗睾丸中的早熟精子发生以及雌性鱼苗中卵睾的形成。