Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, JB Winsløwsvej 17, Odense C, Denmark.
Reprod Toxicol. 2010 Dec;30(4):573-82. doi: 10.1016/j.reprotox.2010.07.009. Epub 2010 Aug 11.
Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, prochloraz) were more potent than the triazoles (epoxiconazole, propiconazole, tebuconazole). The critical mechanism seems to be disturbance of steroid biosynthesis. In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazolemiconazole>ketoconazole>tebuconazole>epoxiconazole>propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase inhibition, since they inhibited the response induced by both 17β-estradiol (miconazole>econazoleketoconazole>prochloraz>tebuconazole>epoxiconazole>propiconazole) and testosterone (econazole>miconazole>prochloraz>ketoconazole>tebuconazole>epoxiconazole>propiconazole). The triazoles were anti-androgenic in an androgen receptor reporter gene assay (epoxiconazole∼tebuconazole>propiconazole). This effect could not be evaluated for the pharmaceutical imidazoles due to cytotoxicity.
广泛使用的唑类抗真菌药物已通过一系列体外检测方法进行了内分泌干扰效应的测试。结果表明，它们都具有内分泌干扰潜力，并可通过多种不同机制发挥作用。总体而言，咪唑类（依康唑、酮康唑、咪康唑、丙环唑）比三唑类（环唑醇、丙硫菌唑、戊唑醇）更为有效。关键的作用机制似乎是干扰甾体生物合成。在 H295R 细胞检测中，唑类药物降低了雌二醇和睾酮的生成，增加了孕酮的浓度，表明它们抑制了将孕酮转化为睾酮的酶。丙环唑的效果最强，其次是依康唑咪康唑>酮康唑>戊唑醇>环唑醇>丙硫菌唑。在 MCF-7 细胞增殖检测中，唑类药物表现出抗雌激素作用，包括抑制芳香酶，因为它们抑制了 17β-雌二醇（咪康唑>依康唑酮康唑>丙环唑>戊唑醇>环唑醇>丙硫菌唑）和睾酮（依康唑>咪康唑>丙环唑>酮康唑>戊唑醇>环唑醇>丙硫菌唑）诱导的反应。三唑类在雄激素受体报告基因检测中具有抗雄激素作用（环唑醇∼戊唑醇>丙硫菌唑）。由于细胞毒性，无法对医药用咪唑类药物进行此评估。
