The presence of cyclic depsipeptide mycotoxins in foods and feedstuffs could potentially cause endocrine disrupting effects on humans and wildlife by their inhibition of active steroidogenesis. Therefore, we attempted to assess the human estrogen receptor (ER) and androgen receptor (AR) agonistic/antagonistic effects of representative cyclic depsipeptide mycotoxins, enniatin A1 (ENN A1), and enniatin B1 (ENN B1), by OECD Performand Based Test Guideline (PBTG) No.455, VM7Luc ER transcriptional activation (TA) assay and OECD TG No. 458, 22Rv1/MMTV_GR-KO AR TA assay. No tested cyclic depsipeptide mycotoxins were found to be ER and AR agonists in VM7Luc ER TA and 22Rv1/MMTV_GR-KO AR TA assays. On the other hand, ENN A1, and ENN B1 exhibited the ER and AR antagonistic effects with IC₃₀ and IC₅₀ values in both TA assays. These two cyclic depsipeptide mycotoxins, which were determined as ER and AR antagonists by two in vitro assays, bound to ERα, and AR. Then ENN A1, and ENN B1 inhibited the dimerization of ERα, and AR. These results, for the first time indicated that ENN A1, and ENN B1 could have potential endocrine disrupting effects mediated by interaction of ERα and AR using international standard testing methods to determine the potential endocrine disrupting chemical.

食品和饲料中存在的环状缩酚肽真菌毒素可能会通过抑制活性类固醇生成而对人类和野生动物造成内分泌干扰影响。因此，我们试图根据 OECD 性能测试指南评估代表性环状缩酚肽真菌毒素 enniatin A1 (ENN A1) 和 enniatin B1 (ENN B1) 的人类雌激素受体 (ER) 和雄激素受体 (AR) 激动/拮抗作用(PBTG) No.455、VM7Luc ER 转录激活 (TA) 检测和 OECD TG No.458、22Rv1/MMTV_GR-KO AR TA 检测。在 VM7Luc ER TA 和 22Rv1/MMTV_GR-KO AR TA 分析中，没有发现测试的环缩肽真菌毒素是 ER 和 AR 激动剂。另一方面，ENN A1 和 ENN B1 表现出 ER 和 AR 拮抗作用，IC ₃₀和 IC ₅₀两种 TA 测定中的值。这两种环状缩肽霉菌毒素通过两种体外试验确定为 ER 和 AR 拮抗剂，与 ERα 和 AR 结合。然后ENN A1和ENN B1抑制ERα和AR的二聚化。这些结果首次表明，ENN A1 和 ENN B1 可能具有潜在的内分泌干扰作用，由 ERα 和 AR 的相互作用介导，使用国际标准测试方法来确定潜在的内分泌干扰化学物质。