Lu Nick Z, Cidlowski John A
Molecular Endocrinology Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, NC 27709, USA.
Trends Cell Biol. 2006 Jun;16(6):301-7. doi: 10.1016/j.tcb.2006.04.005. Epub 2006 May 11.
Glucocorticoids are necessary for life and are essential in all aspects of health and disease as they regulate processes from mitosis to apoptosis, from metabolism to growth and development. However, responses to glucocorticoids vary among individuals, cells and tissues. Recent evidence indicates that multiple glucocorticoid receptor (GR) isoforms are generated from one single GR gene by alternative splicing and alternative translation initiation. These isoforms all have unique tissue distribution patterns and transcriptional regulatory profiles. Furthermore, each is subject to various post-translational modifications that affect receptor function. Thus, increasing evidence suggests that unique GR isoform compositions within cells could determine the cell-specific response to glucocorticoids. Here, we discuss a new molecular model potentially underlying tissue-specific glucocorticoid resistance and selectivity.
糖皮质激素是生命所必需的，在健康和疾病的各个方面都至关重要，因为它们调节从有丝分裂到细胞凋亡、从新陈代谢到生长发育等过程。然而，个体、细胞和组织对糖皮质激素的反应各不相同。最近的证据表明，单个糖皮质激素受体（GR）基因通过可变剪接和可变翻译起始产生多种GR亚型。这些亚型都具有独特的组织分布模式和转录调控谱。此外，每种亚型都受到影响受体功能的各种翻译后修饰。因此，越来越多的证据表明，细胞内独特的GR亚型组成可能决定细胞对糖皮质激素的特异性反应。在此，我们讨论一种可能是组织特异性糖皮质激素抵抗和选择性潜在基础的新分子模型。
