Molecular Metabolic Control, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
J Steroid Biochem Mol Biol. 2010 Oct;122(1-3):10-20. doi: 10.1016/j.jsbmb.2010.02.010. Epub 2010 Feb 17.
Since the discovery of the beneficial effects of adrenocortical extracts for treating adrenal insufficiency more than 80 years ago, glucocorticoids and their cognate, intracellular receptor, the glucocorticoid receptor have been characterized as critical checkpoints in the delicate hormonal control of energy homeostasis in mammals. Whereas physiological levels of glucocorticoids are required for proper metabolic control, aberrant glucocorticoid action has been linked to a variety of pandemic metabolic diseases, such as type II diabetes and obesity. Based on its importance for human health, studies of the molecular mechanisms of within the glucocorticoid signaling axis have become a major focus in biomedical research. In particular, the understanding of tissue-specific functions of the glucocorticoid receptor pathway has been proven to be of substantial value for the development of novel therapies in the treatment of chronic metabolic disorders. Therefore, this review focuses on the consequences of endogenous and experimental modulation of glucocorticoid receptor expression for metabolic homeostasis and dysregulation, particularly emphasizing tissue-specific contributions of the glucocorticoid pathway to the control of energy metabolism.
自 80 多年前发现肾上腺皮质提取物对治疗肾上腺功能不全有益以来，糖皮质激素及其同源的细胞内受体——糖皮质激素受体，被认为是哺乳动物能量平衡的精细激素控制中的关键检查点。虽然生理水平的糖皮质激素是适当代谢控制所必需的，但糖皮质激素的异常作用与各种流行的代谢疾病有关，如 2 型糖尿病和肥胖症。基于其对人类健康的重要性，糖皮质激素信号轴的分子机制研究已成为生物医学研究的一个主要重点。特别是，糖皮质激素受体途径的组织特异性功能的理解已被证明对开发治疗慢性代谢紊乱的新疗法具有重要价值。因此，本综述重点关注内源性和实验性调节糖皮质激素受体表达对代谢稳态和失调的影响，特别强调糖皮质激素途径对控制能量代谢的组织特异性贡献。
