Neurological and Endocrine Toxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Neurological and Endocrine Toxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Neurotoxicol Teratol. 2023 Nov-Dec;100:107303. doi: 10.1016/j.ntt.2023.107303. Epub 2023 Sep 28.
Identifying xenobiotics that interrupt the thyroid axis has significant public health implications, given that thyroid hormones are required for brain development. As such, some developmental and reproductive toxicology (DART) studies now require or recommend serum total thyroxine (T4) measurements in pregnant, lactating, and developing rats. However, serum T4 concentrations are normally low in the fetus and pup which makes quantification difficult. These challenges can be circumvented by technologies like mass spectrometry, but these approaches are expensive and not always widely available. To demonstrate the feasibility of measuring T4 using a commercially available assay, we examine technical replicates of rat serum samples measured both by liquid chromatography mass spectrometry (LC/MS/MS) and radioimmunoassay (RIA). These samples were obtained from rats on gestational day 20 (dams and fetuses) or postnatal day 5 (pups), following maternal exposure to the goitrogen propylthiouracil (0-3 ppm) to incrementally decrease T4. We show that with assay modification, it is possible to measure serum T4 using low sample volumes (25-50 μL) by an RIA, including in the GD20 fetus exposed to propylthiouracil. This proof-of-concept study demonstrates the technical feasibility of measuring serum T4 in DART studies.
由于甲状腺激素是大脑发育所必需的，因此，识别会干扰甲状腺轴的外源性化学物质具有重要的公共卫生意义。正因为如此，一些发育和生殖毒理学 (DART) 研究现在要求或推荐对怀孕、哺乳期和发育中的大鼠进行血清总甲状腺素 (T4) 测量。然而，胎儿和幼崽的血清 T4 浓度通常较低，这使得定量变得困难。这些挑战可以通过质谱等技术来规避，但这些方法昂贵且并非总是广泛可用。为了证明使用市售试剂盒测量 T4 的可行性，我们检查了通过液相色谱-质谱联用 (LC/MS/MS) 和放射免疫分析 (RIA) 测量的大鼠血清样本的技术重复。这些样本来自于妊娠第 20 天 (母体和胎儿) 或产后第 5 天 (幼崽) 的母体暴露于致甲状腺肿剂丙基硫氧嘧啶 (0-3ppm) 的大鼠，以逐渐降低 T4。我们表明，通过对试剂盒进行修改，通过 RIA 可以使用低样本量 (25-50μL) 测量血清 T4，包括暴露于丙基硫氧嘧啶的 GD20 胎儿。这项概念验证研究证明了在 DART 研究中测量血清 T4 的技术可行性。
