Exploring novel biomarkers for endocrine disruptor exposure: insights into extra-nuclear signaling pathways of estrogen and androgen receptors

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2026-03-01 Epub Date: 2026-01-23 DOI:10.1016/j.etap.2026.104949

Manuela Cipolletti , Ilaria Campesi , Marco Pellegrini , Marco Fiocchetti , Filippo Acconcia , Maria Marino

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Abstract

Synthetic chemicals classified as endocrine disruptors (EDs) pose health risks by interfering with sex-steroid hormone signaling. This study evaluated bisphenol A (BPA) for its effects on ERα, ERβ, and AR expression and extranuclear signaling, including ERα phosphorylation, in human monocytes from healthy male and female donors, and assessed ten additional chemicals in ERα-positive breast cancer cell lines (MCF-7, T47D). BPA increased ERα phosphorylation in both male and female monocytes without altering receptor levels, while modulating downstream signaling in a sex-dependent manner and attenuating DHT- or E2-induced effects. The ten other chemicals similarly enhanced ERα phosphorylation, often independently of direct receptor binding. These findings indicate that ERα phosphorylation is a sensitive, early marker of ED activity across immune and epithelial cells and support its use as a receptor-proximal endpoint to complement conventional transcription-based assays in next-generation ED screening strategies.

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探索内分泌干扰物暴露的新生物标志物：对雌激素和雄激素受体核外信号通路的见解

被归类为内分泌干扰物（EDs）的合成化学品通过干扰性类固醇激素信号而构成健康风险。本研究评估了双酚A （BPA）对来自健康男性和女性供体的人单核细胞中ERα、ERβ、AR表达和核外信号传导的影响，包括ERα磷酸化，并评估了ERα阳性乳腺癌细胞系（MCF-7, T47D）中的十种其他化学物质。BPA在不改变受体水平的情况下增加了雄性和雌性单核细胞的ERα磷酸化，同时以性别依赖的方式调节下游信号，并减弱DHT或e2诱导的作用。其他十种化学物质类似地增强ERα磷酸化，通常独立于直接受体结合。这些发现表明，ERα磷酸化是免疫细胞和上皮细胞中ED活性的一个敏感的早期标记，并支持其作为受体近端终点，在下一代ED筛查策略中补充传统的基于转录的检测。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.