Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
J Hazard Mater. 2024 Dec 5;480:135841. doi: 10.1016/j.jhazmat.2024.135841. Epub 2024 Sep 19.
Parabens are preservatives used in personal care products, cosmetics, and pharmaceuticals. Steroid 5α-reductase 1 (SRD5A1) catalyzes the conversion of testosterone to dihydrotestosterone and is present in the brain, contributing to neurosteroid production. This study aimed to assess the effects of nine paraben preservatives on SRD5A1 in human SF126 glioblastoma cell and rat brain microsomes, particularly focusing on dihydrotestosterone production in SF126 cells. The results showed that methyl, ethyl, propyl, butyl, hexyl, heptyl, nonyl, phenyl, and benzyl paraben inhibited human SRD5A1, with nonylparaben having the strongest effect (7.59 μM). Additionally, kinetic analysis indicated that parabens acted as mixed/noncompetitive inhibitors, leading to a significant decrease in dihydrotestosterone production in SF126 cells. While rat SRD5A1 exhibited lower sensitivity to parabens, docking analysis revealed that parabens bind to the NADPH-binding site of both human and rat SRD5A1. In conclusion, these results highlight the inhibitory effects of paraben preservatives on SRD5A1 and elucidate their binding mechanisms, underscoring their role in hormone production.
对羟基苯甲酸酯是个人护理产品、化妆品和药物中使用的防腐剂。甾体 5α-还原酶 1（SRD5A1）催化睾酮转化为二氢睾酮，并存在于大脑中，有助于神经甾体的产生。本研究旨在评估 9 种对羟基苯甲酸酯防腐剂对人 SF126 神经胶质瘤细胞和大鼠脑微粒体中 SRD5A1 的影响，特别关注 SF126 细胞中二氢睾酮的产生。结果表明，甲基、乙基、丙基、丁基、己基、庚基、壬基、苯基和苄基对羟基苯甲酸酯抑制了人 SRD5A1，其中壬基对羟基苯甲酸酯的抑制作用最强（7.59μM）。此外，动力学分析表明，对羟基苯甲酸酯作为混合/非竞争性抑制剂，导致 SF126 细胞中二氢睾酮的产生显著减少。虽然大鼠 SRD5A1 对对羟基苯甲酸酯的敏感性较低，但对接分析表明，对羟基苯甲酸酯结合到人和大鼠 SRD5A1 的 NADPH 结合位点。总之，这些结果强调了对羟基苯甲酸酯防腐剂对 SRD5A1 的抑制作用，并阐明了它们的结合机制，突出了它们在激素产生中的作用。
