Previously, levonorgestrel (LNG) has been shown to be an endocrine disruptor of the amphibian thyroid system. In the present study, we investigated whether anti-thyroidal effects are a common property of progestins other than LNG. Premetamorphic Xenopus laevis tadpoles were exposed to norethisterone (NET) and dienogest DIE (each at 0.1–10 nM) and LNG (10 nM) until completion of metamorphosis. LNG and NET at all concentrations caused a significant developmental retardation whereas DIE did not impair time to metamorphosis. In LNG and 10 nM NET exposed animals, tsh mRNA levels increased considerably later than the developmental delay occurred and thyroid histopathology showed no signs of TSH-hyperstimulation. Instead, thyroid glands from these treatments appeared inactive in producing thyroid hormones. Thyroidal transcript levels of dio2 and dio3 were increased by treatments with LNG and NET at 1 nM and 10 nM, whereas iyd mRNA was reduced by LNG and 10 nM NET. Expression of slc5α5 was not changed by any treatment. Effects of DIE differed from those induced by LNG and NET. No developmental delay was measurable; however, tshβ and dio2 mRNAs were increased in pituitary glands of tadpoles exposed to 1.0 nM and 10 nM DIE. Thyroid histopathology displayed no abnormalities and thyroidal mRNA expression of the genes analyzed (slc5α5, iyd, dio2, dio3) was not changed by DIE. Overall, our results provide evidence that the anti-thyroidal effects already known from LNG are also present in another progestin, namely NET, even at environmentally relevant concentrations. In conclusion we suggest that progestins do not only pose an environmental risk in terms of their impact on reproductive success of aquatic vertebrates, but also with respect to their anti-thyroidal properties affecting amphibian metamorphosis.

以前，左炔诺孕酮（LNG）已被证明是两栖甲状腺系统的内分泌干扰物。在本研究中，我们调查了除LNG以外的其他孕激素是否都具有抗甲状腺作用。前变态非洲爪蟾X暴露于炔诺酮（NET）和双歧杆菌DIE（每个剂量为0.1-10 nM）和LNG（10 nM），直到变态完成。在所有浓度下，LNG和NET都会导致显着的发育迟缓，而DIE不会损害变质时间。在LNG和10 nM NET暴露的动物中，tshmRNA水平显着晚于发育延迟发生，并且甲状腺组织病理学没有显示TSH过度刺激的迹象。取而代之的是，来自这些治疗方法的甲状腺在产生甲状腺激素方面似乎没有活性。通过在1 nM和10 nM下用LNG和NET处理，可增加dio2和dio3的甲状腺转录水平，而通过LNG和10 nM NET处理可降低iyd mRNA的表达。slc5α5的表达未通过任何处理改变。DIE的效果不同于LNG和NET的效果。没有可测量的发育延迟；但是，tshβ和dio2暴露于1.0 nM和10 nM DIE的t的垂体腺中mRNA升高。甲状腺组织病理学未见异常，DIE未改变分析基因（slc5α5，iyd，dio2，dio3）的甲状腺mRNA表达。总体而言，我们的结果提供了证据，即从LNG已知的抗甲状腺作用也存在于另一种孕激素（即NET）中，即使在与环境相关的浓度下也是如此。总之，我们建议孕激素不仅对水生脊椎动物的繁殖成功产生影响，而且对影响两栖动物变态的抗甲状腺特性也构成环境风险。