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肌醇对多囊卵巢综合征卵泡的影响是否涉及细胞骨架调节?

Does myo-inositol effect on PCOS follicles involve cytoskeleton regulation?

作者信息

Bizzarri Mariano, Cucina Alessandra, Dinicola Simona, Harrath Abdel Halim, Alwasel Saleh H, Unfer Vittorio, Bevilacqua Arturo

机构信息

Department of Experimental Medicine, Sapienza University of Rome, viale Regina Elena 324, 00161 Rome, Italy; Systems Biology Group Lab, Sapienza University of Rome, Rome, Italy.

Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Via A. Scarpa 14, 00161 Rome, Italy; Azienda Policlinico Umberto I, viale del Policlinico 155, 00161 Rome, Italy.

出版信息

Med Hypotheses. 2016 Jun;91:1-5. doi: 10.1016/j.mehy.2016.03.014. Epub 2016 Apr 4.

Abstract

Inositol metabolism is severely impaired in follicles obtained from cystic ovaries, leading to deregulated insulin transduction and steroid synthesis. On the contrary, inositol administration to women suffering from polycystic ovary syndrome (PCOS) has been proven to efficiently counteract most of the clinical hallmarks displayed by PCOS patients, including insulin resistance, hyperandrogenism and oligo-amenorrhea. We have recently observed that myo-inositol induces significant changes in cytoskeletal architecture of breast cancer cells, by modulating different biochemical pathways, eventually modulating the epithelial-mesenchymal transition. We hypothesize that inositol and its monophosphate derivatives, besides their effects on insulin transduction, may efficiently revert histological and functional features of cystic ovary by inducing cytoskeleton rearrangements. We propose an experimental model that could address not only whether inositol modulates cytoskeleton dynamics in both normal and cystic ovary cells, but also whether this effect may interfere with ovarian steroidogenesis. A more compelling understanding of the mechanisms of action of inositol (and its derivatives) would greatly improve its therapeutic utilization, by conferring to current treatments a well-grounded scientific rationale.

摘要

在从多囊卵巢获取的卵泡中,肌醇代谢严重受损,导致胰岛素转导和类固醇合成失调。相反,已证明对多囊卵巢综合征(PCOS)患者给予肌醇可有效对抗PCOS患者表现出的大多数临床特征,包括胰岛素抵抗、高雄激素血症和月经稀发。我们最近观察到,肌醇通过调节不同的生化途径,最终调节上皮-间质转化,从而诱导乳腺癌细胞的细胞骨架结构发生显著变化。我们假设,肌醇及其单磷酸衍生物除了对胰岛素转导有影响外,还可能通过诱导细胞骨架重排有效恢复多囊卵巢的组织学和功能特征。我们提出了一个实验模型,该模型不仅可以解决肌醇是否调节正常和多囊卵巢细胞中的细胞骨架动力学问题,还可以解决这种效应是否会干扰卵巢类固醇生成的问题。更深入地了解肌醇(及其衍生物)的作用机制将通过为当前治疗提供有充分依据的科学原理,极大地改善其治疗应用。

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