Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Lokmanya Tilak Municipal Medical College, Mumbai, India.
Mol Cell Proteomics. 2023 Jan;22(1):100478. doi: 10.1016/j.mcpro.2022.100478. Epub 2022 Dec 5.
To date, very few mass spectrometry (MS)-based proteomics studies are available on the anterior and posterior lobes of the pituitary. In the past, MS-based investigations have focused exclusively on the whole pituitary gland or anterior pituitary lobe. In this study, for the first time, we performed a deep MS-based analysis of five anterior and five posterior matched lobes to build the first lobe-specific pituitary proteome map, which documented 4090 proteins with isoforms, mostly mapped into chromosomes 1, 2, and 11. About 1446 differentially expressed significant proteins were identified, which were studied for lobe specificity, biological pathway enrichment, protein-protein interaction, regions specific to comparison of human brain and other neuroendocrine glands from Human Protein Atlas to identify pituitary-enriched proteins. Hormones specific to each lobe were also identified and validated with parallel reaction monitoring-based target verification. The study identified and validated hormones, growth hormone and thyroid-stimulating hormone subunit beta, exclusively to the anterior lobe whereas oxytocin-neurophysin 1 and arginine vasopressin to the posterior lobe. The study also identified proteins POU1F1 (pituitary-specific positive transcription factor 1), POMC (pro-opiomelanocortin), PCOLCE2 (procollagen C-endopeptidase enhancer 2), and NPTX2 (neuronal pentraxin-2) as pituitary-enriched proteins and was validated for their lobe specificity using parallel reaction monitoring. In addition, three uPE1 proteins, namely THEM6 (mesenchymal stem cell protein DSCD75), FSD1L (coiled-coil domain-containing protein 10), and METTL26 (methyltransferase-like 26), were identified using the NeXtProt database, and depicted tumor markers S100 proteins having high expression in the posterior lobe. In summary, the study documents the first matched anterior and posterior pituitary proteome map acting as a reference control for a better understanding of functional and nonfunctional pituitary adenomas and extrapolating the aim of the Human Proteome Project towards the investigation of the proteome of life.
迄今为止，关于垂体前叶和后叶的基于质谱（MS）的蛋白质组学研究非常少。过去，基于 MS 的研究仅集中在整个垂体或垂体前叶。在这项研究中，我们首次对五个前叶和五个后叶进行了深入的 MS 分析，以构建第一个叶特异性垂体蛋白质组图谱，该图谱记录了 4090 个带有同工型的蛋白质，主要映射到染色体 1、2 和 11。鉴定出约 1446 个差异表达的有意义的蛋白质，研究了它们的叶特异性、生物途径富集、蛋白质-蛋白质相互作用、人类蛋白质图谱中比较人脑和其他神经内分泌腺的区域特异性，以鉴定垂体富集蛋白。还使用平行反应监测的靶验证鉴定和验证了特定于每个叶的激素。该研究鉴定和验证了激素，生长激素和促甲状腺激素亚基β，仅在前叶特异性，而催产素神经肽 1 和精氨酸血管加压素在后叶特异性。该研究还鉴定了蛋白质 POU1F1（垂体特异性正转录因子 1）、POMC（促阿黑皮素原）、PCOLCE2（前胶原 C-末端肽酶增强子 2）和 NPTX2（神经元五肽-2）作为垂体富集蛋白，并使用平行反应监测验证了它们的叶特异性。此外，使用 NeXtProt 数据库鉴定了三种 uPE1 蛋白，即 THEM6（间充质干细胞蛋白 DSCD75）、FSD1L（卷曲螺旋结构域蛋白 10）和 METTL26（甲基转移酶样 26），并描绘了后叶高表达的肿瘤标志物 S100 蛋白。总之，该研究记录了第一个匹配的垂体前叶和后叶蛋白质组图谱，作为更好地理解功能性和非功能性垂体腺瘤的参考对照，并将人类蛋白质组计划的目标扩展到生命蛋白质组的研究。
