State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Chemosphere. 2013 Jan;90(3):1227-35. doi: 10.1016/j.chemosphere.2012.09.056. Epub 2012 Oct 17.
1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(γ)-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) are widely used in personal care products. Previous studies showed that HHCB and AHTN can be found in various environmental matrices and have potential endocrine disrupting effects. However, the effects on adrenocortical function of HHCB and AHTN are not fully understood. This study evaluated the influences of HHCB and AHTN on seven steroid hormones (progesterone, aldosterone, cortisol, 17α-OH-progesterone, androstenedione, 17β-estradiol, and testosterone) and 10 genes involved in steroidogenic pathways (HMGR, StAR, CYP11A1, 3βHSD2, CYP17, CYP21, CYP11B1, CYP11B2, 17βHSD, and CYP19) using the H295R cell line in the absence and presence of 8-Br-cAMP. MC2R transcription on the cell membrane was also examined to further investigate the effects of HHCB and AHTN on adrenal steroidogenesis. The results demonstrated that HHCB and AHTN could inhibit progesterone and cortisol production mainly by the suppression of 3βHSD2 and CYP21. Meanwhile, high concentrations of AHTN can affect the sensitivity of H295R cells to ACTH by disrupting MC2R transcription. Overall, the results indicate that high concentrations of HHCB and AHTN can affect steroidogenesis in vitro using the H295R cell line.
1,3,4,6,7,8-六氢-4,6,6,7,8,8-六甲基环戊基-(γ)-2-苯并吡喃（HHCB）和 7-乙酰基-1,1,3,4,4,6-六甲基-1,2,3,4-四氢萘（AHTN）广泛应用于个人护理产品。先前的研究表明，HHCB 和 AHTN 可以在各种环境基质中被发现，并具有潜在的内分泌干扰作用。然而，HHCB 和 AHTN 对肾上腺皮质功能的影响尚不完全清楚。本研究评估了 HHCB 和 AHTN 对七种甾体激素（孕酮、醛固酮、皮质醇、17α-OH-孕酮、雄烯二酮、17β-雌二醇和睾酮）和 10 个参与甾体生成途径的基因（HMGR、StAR、CYP11A1、3βHSD2、CYP17、CYP21、CYP11B1、CYP11B2、17βHSD 和 CYP19）的影响，使用 H295R 细胞系在缺乏和存在 8-Br-cAMP 的情况下进行。还检查了细胞膜上的 MC2R 转录，以进一步研究 HHCB 和 AHTN 对肾上腺甾体生成的影响。结果表明，HHCB 和 AHTN 主要通过抑制 3βHSD2 和 CYP21 来抑制孕酮和皮质醇的产生。同时，高浓度的 AHTN 可以通过破坏 MC2R 转录来影响 H295R 细胞对 ACTH 的敏感性。总体而言，这些结果表明，高浓度的 HHCB 和 AHTN 可以在体外使用 H295R 细胞系影响甾体生成。
