Department of Biological Sciences, Morphophysiology and Pathology Sector, Federal University of São Paulo (UNIFESP), Diadema, SP, Brazil.
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Adv Exp Med Biol. 2024;1443:187-209. doi: 10.1007/978-3-031-50624-6_10.
Innovative techniques such as the "omics" can be a powerful tool for the understanding of intracellular pathways involved in homeostasis maintenance and identification of new potential therapeutic targets against endocrine-metabolic disorders. Over the last decades, proteomics has been extensively applied in the study of a wide variety of human diseases, including those involving the endocrine system. Among the most endocrine-related disorders investigated by proteomics in humans are diabetes mellitus and thyroid, pituitary, and reproductive system disorders. In diabetes, proteins implicated in insulin signaling, glucose metabolism, and β-cell activity have been investigated. In thyroid diseases, protein expression alterations were described in thyroid malignancies and autoimmune thyroid illnesses. Additionally, proteomics has been used to investigate the variations in protein expression in adrenal cancers and conditions, including Cushing's syndrome and Addison's disease. Pituitary tumors and disorders including acromegaly and hypopituitarism have been studied using proteomics to examine changes in protein expression. Reproductive problems such as polycystic ovarian syndrome and endometriosis are two examples of conditions where alterations in protein expression have been studied using proteomics. Proteomics has, in general, shed light on the molecular underpinnings of many endocrine-related illnesses and revealed promising biomarkers for both their detection and treatment. The capacity of proteomics to thoroughly and objectively examine complex protein mixtures is one of its main benefits. Mass spectrometry (MS) is a widely used method that identifies and measures proteins based on their mass-to-charge ratio and their fragmentation pattern. MS can perform the separation of proteins according to their physicochemical characteristics, such as hydrophobicity, charge, and size, in combination with liquid chromatography. Other proteomics techniques include protein arrays, which enable the simultaneous identification of several proteins in a single assay, and two-dimensional gel electrophoresis (2D-DIGE), which divides proteins depending on their isoelectric point and molecular weight. This chapter aims to summarize the most relevant proteomics data from targeted tissues, as well as the daily rhythmic variation of relevant biomarkers in both physiological and pathophysiological conditions within the involved endocrine system, especially because the actual modern lifestyle constantly imposes a chronic unentrained condition, which virtually affects all the circadian clock systems within human's body, being also correlated with innumerous endocrine-metabolic diseases.
创新技术,如“组学”,可以成为理解参与内稳态维持的细胞内途径的强大工具,并确定针对内分泌代谢疾病的新的潜在治疗靶点。在过去的几十年中,蛋白质组学已广泛应用于各种人类疾病的研究,包括涉及内分泌系统的疾病。在蛋白质组学研究的与内分泌相关的疾病中,糖尿病和甲状腺、垂体和生殖系统疾病最为常见。在糖尿病中,研究了涉及胰岛素信号、葡萄糖代谢和β细胞活性的蛋白质。在甲状腺疾病中,描述了甲状腺恶性肿瘤和自身免疫性甲状腺疾病中的蛋白质表达改变。此外,蛋白质组学还用于研究肾上腺癌和包括库欣综合征和艾迪生病在内的疾病中蛋白质表达的变化。使用蛋白质组学研究垂体肿瘤和疾病,如肢端肥大症和垂体功能减退症,以检查蛋白质表达的变化。生殖问题,如多囊卵巢综合征和子宫内膜异位症,是使用蛋白质组学研究蛋白质表达改变的两个例子。蛋白质组学总体上揭示了许多与内分泌相关疾病的分子基础,并为它们的检测和治疗提供了有前途的生物标志物。蛋白质组学的一个主要优点是能够全面、客观地研究复杂的蛋白质混合物。质谱 (MS) 是一种广泛使用的方法,它根据蛋白质的质荷比和其碎片化模式来识别和测量蛋白质。MS 可以与液相色谱结合,根据蛋白质的物理化学特性,如疏水性、电荷和大小,对蛋白质进行分离。其他蛋白质组学技术包括蛋白质微阵列,它可以在单次测定中同时识别几种蛋白质,以及二维凝胶电泳 (2D-DIGE),它可以根据蛋白质的等电点和分子量对蛋白质进行分类。本章旨在总结来自靶向组织的最相关蛋白质组学数据,以及相关生物标志物在涉及的内分泌系统中生理和病理生理条件下的日常节律变化,特别是因为现代生活方式不断强加一种慢性非同步状态,几乎影响人体所有的生物钟系统,也与无数的内分泌代谢疾病相关。