Stein T Peter
Rowan-Virtua School of Translational Biomedical Engineering and Sciences and School of Osteopathic Medicine, 2 Medical Center Drive, Stratford, NJ 08084, USA.
Biomedicines. 2024 Nov 25;12(12):2678. doi: 10.3390/biomedicines12122678.
Autism spectrum disorders (ASDs), attention-deficit disorder (ADHD), Parkinson's disease (PD), polycystic ovary disease (PCOS), and Alzheimer's disease (AD) have all been linked to exposure to bisphenol A (BPA).
This paper is a review and discussion of the published literature.
Animal studies have shown BPA to be a broad-spectrum endocrine disruptor. BPA is metabolized via the glucuronidation pathway, which involves the addition of glucose to the target molecule, and is catalyzed by uridine 5'-diphospho-glucuronosyltransferases (UGTs). Evidence of compromised glucuronidation has been found for ASD, DHD, PD, and PCOS. Genetic polymorphisms that alter the catalytic activity of the UGTs and efflux transporters involved are common. There are two ways to interpret the findings of associations between BPA glucuronidation efficiency and disease, a 'direct' pathway and an 'indirect' pathway. With the 'direct' pathway, free BPA is the actual causative agent. Compromised BPA detoxification leads to higher concentrations of free BPA in vulnerable tissues. Decreased BPA detoxification leads to increased exposure of vulnerable tissues to free BPA, where it can function as an endocrine disruptor. With the 'indirect' pathway, BPA is not the causative agent. BPA serves as a marker for the decreased glucuronidation efficiency of another unknown compound of endogenous origin detoxified by a similar combination of UGTs and efflux transporters as BPA. It is this compound(s), acting as an endocrine disruptor, that leads to a metabolic environment that favors disease development over an extended time period.
A review of the existing literature supports the indirect 'marker' hypothesis over the 'direct' hypothesis.
自闭症谱系障碍（ASD）、注意力缺陷多动障碍（ADHD）、帕金森病（PD）、多囊卵巢综合征（PCOS）和阿尔茨海默病（AD）都与双酚A（BPA）暴露有关。
本文是对已发表文献的综述与讨论。
动物研究表明BPA是一种广谱内分泌干扰物。BPA通过葡萄糖醛酸化途径代谢，该途径涉及将葡萄糖添加到目标分子上，并由尿苷5'-二磷酸葡萄糖醛酸基转移酶（UGTs）催化。已发现ASD、DHD、PD和PCOS存在葡萄糖醛酸化受损的证据。改变所涉及的UGTs和外排转运蛋白催化活性的基因多态性很常见。有两种方式来解释BPA葡萄糖醛酸化效率与疾病之间关联的研究结果，即“直接”途径和“间接”途径。在“直接”途径中，游离BPA是实际致病因子。BPA解毒受损导致脆弱组织中游离BPA浓度升高。BPA解毒能力下降导致脆弱组织暴露于游离BPA的量增加，在那里它可作为内分泌干扰物发挥作用。在“间接”途径中，BPA不是致病因子。BPA作为另一种内源性未知化合物葡萄糖醛酸化效率降低的标志物，该化合物通过与BPA类似的UGTs和外排转运蛋白组合进行解毒。正是这种作为内分泌干扰物的化合物，导致了一种在较长时间内有利于疾病发展的代谢环境。
对现有文献的综述支持“间接”“标志物”假说而非“直接”假说。
