Joint Research Division, Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH), Heidelberg University, Network Aging Research, University Hospital Heidelberg, Germany.
Mol Cell Endocrinol. 2013 Nov 5;380(1-2):65-78. doi: 10.1016/j.mce.2013.03.007. Epub 2013 Mar 20.
In the past decades, glucocorticoid (GC) hormones and their cognate, intracellular receptor, the glucocorticoid receptor (GR), have been well established as critical checkpoints in mammalian energy homeostasis. Whereas many aspects in healthy nutrient metabolism require physiological levels and/or action of GC, aberrant GC/GR signalling has been linked to severe metabolic dysfunction, including obesity, insulin resistance and type 2 diabetes. Consequently, studies of the molecular mechanisms within the GC signalling axis have become a major focus in biomedical research, up-to-date particularly focusing on systemic glucose and lipid handling. However, with the availability of novel high throughput technologies and more sophisticated metabolic phenotyping capabilities, as-yet non-appreciated, metabolic functions of GC have been recently discovered, including regulatory roles of the GC/GR axis in protein and bile acid homeostasis as well as metabolic inter-organ communication. Therefore, this review summarises recent advances in GC/GR biology, and summarises findings relevant for basic and translational metabolic research.
在过去几十年中，糖皮质激素（GC）及其同源的细胞内受体，糖皮质激素受体（GR），已被确立为哺乳动物能量平衡的关键检查点。尽管健康营养代谢的许多方面需要 GC 的生理水平和/或作用，但异常的 GC/GR 信号已与严重的代谢功能障碍相关，包括肥胖、胰岛素抵抗和 2 型糖尿病。因此，GC 信号轴内的分子机制研究已成为生物医学研究的主要焦点，目前特别关注全身葡萄糖和脂质处理。然而，随着新型高通量技术和更复杂的代谢表型分析能力的出现，GC 的尚未被认识到的代谢功能最近被发现，包括 GC/GR 轴在蛋白质和胆汁酸稳态以及代谢器官间通讯中的调节作用。因此，本文总结了 GC/GR 生物学的最新进展，并总结了与基础和转化代谢研究相关的发现。
