Biology, The Life Science Center, School of Science and Technology, Örebro University, SE-701 82, Örebro, Sweden.
Department of Chemistry, Umeå University, SE-901 87, Umeå, Sweden.
Reprod Toxicol. 2021 Jun;102:43-55. doi: 10.1016/j.reprotox.2021.04.002. Epub 2021 Apr 10.
The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). in vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers α and β, a 1:1 mixture of γ and δ, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated mice were used to study the androgenic effects of TBECHαβ and TBECHγδ while the antagonistic effects of DPTE were studied in non-castrated mice. We observed that testosterone and TBECHγδ increased body and prostate weights while TBECHαβ affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECHγδ group comparable to those in testosterone group while alterations in the TBECHαβ group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECHγδ reversed several of these changes. Testosterone and TBECHγδ also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECHγδ and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function.
溴化阻燃剂（BFRs），1,2-二溴-4-（1,2-二溴乙基）环己烷（TBECH）和 2,3-二溴丙基-2,4,6-三溴苯基醚（DPTE）与雄激素受体（AR）结合。体外生物测定表明，TBECH 是一种有效的雄激素激动剂，而 DPTE 是一种有效的 AR 拮抗剂。TBECH 和 DPTE 均可改变与 AR 调节相关的基因表达。然而，TBECH 和 DPTE 是否会影响前列腺仍有待确定。出于这个原因，我们用 TBECH 对映体 α 和 β 的 1:1 混合物、γ 和 δ 的 1:1 混合物以及 DPTE 处理 CD1 小鼠，检测它们对前列腺生长、组织学和基因表达谱的影响。去势小鼠用于研究 TBECHαβ 和 TBECHγδ 的雄激素作用，而 DPTE 的拮抗作用则在非去势小鼠中进行研究。我们观察到，睾酮和 TBECHγδ 增加了体重和前列腺重量，而 TBECHαβ 对两者均无影响；DPTE 对体重没有影响，但大大降低了前列腺重量。前列腺的组织形态计量学分析显示，TBECHγδ 组的上皮和腺体改变与睾酮组相似，而 TBECHαβ 组的改变则不那么明显。DPTE 表现出类似于去势的雄激素拮抗剂活性。前列腺的转录谱受去势和睾酮以及 TBECHγδ 的暴露而改变，TBECHγδ 逆转了其中的一些变化。睾酮和 TBECHγδ 还调节了几个与前列腺生长和癌症有关的雄激素反应基因的表达。虽然 DPTE 导致前列腺重量急剧下降，但它仅影响少数几个基因。结果表明，TBECHγδ 和 DPTE 对人类健康有很大的关注，因为它们可能导致前列腺生长、组织学和功能的变化。
