肝细胞中的糖皮质激素受体功能对于促进出生后身体生长至关重要。
Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth.
作者信息
Tronche François, Opherk Christian, Moriggl Richard, Kellendonk Christoph, Reimann Andreas, Schwake Lukas, Reichardt Holger M, Stangl Katharina, Gau Daniel, Hoeflich Andreas, Beug Hartmut, Schmid Wolfgang, Schütz Günther
机构信息
Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
出版信息
Genes Dev. 2004 Mar 1;18(5):492-7. doi: 10.1101/gad.284704.
Abstract
Mice carrying a hepatocyte-specific inactivation of the glucorticoid receptor (GR) gene show a dramatic reduction in body size. Growth hormone signaling mediated by the Stat5 transcription factors is impaired. We show that Stat5 proteins physically interact with GR and GR is present in vivo on Stat5-dependent IGF-I and ALS regulatory regions. Interestingly, mice with a DNA-binding-deficient GR but an unaltered ability to interact with STAT5 (GR(dim/dim)) have a normal body size and normal levels of Stat5-dependent mRNAs. These findings strongly support the model in which GR acts as a coactivator for Stat5-dependent transcription upon GH stimulation and reveal an essential role of hepatic GR in the control of body growth.
摘要
携带糖皮质激素受体（GR）基因肝细胞特异性失活的小鼠体型显著减小。由Stat5转录因子介导的生长激素信号传导受损。我们发现Stat5蛋白与GR发生物理相互作用，并且GR在体内存在于Stat5依赖性IGF-I和ALS调控区域。有趣的是，具有DNA结合缺陷型GR但与STAT5相互作用能力未改变的小鼠（GR(dim/dim)）具有正常体型和正常水平的Stat5依赖性mRNA。这些发现有力地支持了GR在生长激素刺激下作为Stat5依赖性转录的共激活因子发挥作用的模型，并揭示了肝脏GR在控制身体生长中的重要作用。
相似文献
1
Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth.肝细胞中的糖皮质激素受体功能对于促进出生后身体生长至关重要。
Genes Dev. 2004 Mar 1;18(5):492-7. doi: 10.1101/gad.284704.
2
Expression level-dependent contribution of glucocorticoid receptor domains for functional interaction with STAT5.糖皮质激素受体结构域对与STAT5功能相互作用的表达水平依赖性贡献
Mol Cell Biol. 2001 May;21(9):3266-79. doi: 10.1128/MCB.21.9.3266-3279.2001.
3
Mechanism of interaction between the glucocorticoid receptor and Stat5: role of DNA-binding.糖皮质激素受体与Stat5之间的相互作用机制：DNA结合的作用
Immunobiology. 1997 Dec;198(1-3):112-23. doi: 10.1016/S0171-2985(97)80032-0.
4
Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects.催乳素、生长激素和表皮生长因子在乳腺组织的不同区域激活信号转导和转录激活因子5（Stat5），并发挥不同但又重叠的发育效应。
Dev Biol. 2001 Jan 1;229(1):163-75. doi: 10.1006/dbio.2000.9961.
5
Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression.肝细胞中糖皮质激素受体与Stat5的直接相互作用控制体型和成熟相关基因的表达。
Genes Dev. 2007 May 15;21(10):1157-62. doi: 10.1101/gad.426007.
6
Growth hormone increases Stat5 and Stat1 expression in lactating goat mammary gland: a specific effect compared to milking frequency.生长激素可增加泌乳山羊乳腺中Stat5和Stat1的表达：与挤奶频率相比的特异性作用。
Domest Anim Endocrinol. 2004 Nov;27(4):363-78. doi: 10.1016/j.domaniend.2004.04.002.
7
Growth hormone-mediated janus associated kinase-signal transducers and activators of transcription signaling in the growth hormone-resistant potassium-deficient rat.生长激素抵抗性缺钾大鼠中生长激素介导的janus相关激酶-信号转导子和转录激活子信号通路
J Am Soc Nephrol. 2004 Sep;15(9):2299-306. doi: 10.1097/01.ASN.0000137885.63580.92.
8
Functional interactions between Stat5 and the glucocorticoid receptor.信号转导及转录激活因子5（Stat5）与糖皮质激素受体之间的功能相互作用。
Nature. 1996 Oct 24;383(6602):726-8. doi: 10.1038/383726a0.
9
Alterations in growth hormone receptor abundance regulate growth hormone signaling in murine obstructive cholestasis.生长激素受体丰度的改变调节小鼠梗阻性胆汁淤积中的生长激素信号传导。
Am J Physiol Gastrointest Liver Physiol. 2005 May;288(5):G986-93. doi: 10.1152/ajpgi.00287.2004. Epub 2004 Dec 16.
10
Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b).细胞因子信号转导抑制因子2（SOCS-2）缺陷小鼠的生长增强依赖于信号转导子和转录激活子5b（STAT5b）。
Mol Endocrinol. 2002 Jun;16(6):1394-406. doi: 10.1210/mend.16.6.0845.
引用本文的文献
1
A cross-tissue transcriptomic approach decodes glucocorticoid receptor-dependent links to human metabolic phenotypes.一种跨组织转录组学方法解码了糖皮质激素受体依赖性与人类代谢表型的关联。
BMC Genomics. 2025 May 9;26(1):462. doi: 10.1186/s12864-025-11676-w.
2
Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis.核受体辅阻遏物非经典地驱动肝糖异生中糖皮质激素受体依赖性的激活。
Nat Metab. 2024 May;6(5):825-836. doi: 10.1038/s42255-024-01029-4. Epub 2024 Apr 15.
3
Adipocyte STAT5 (signal transducer and activator of transcription 5) is not required for glucocorticoid-induced metabolic dysfunction.脂肪细胞 STAT5（信号转导和转录激活因子 5）对于糖皮质激素诱导的代谢功能障碍不是必需的。
Am J Physiol Endocrinol Metab. 2023 Nov 1;325(5):E438-E447. doi: 10.1152/ajpendo.00116.2023. Epub 2023 Sep 13.
4
Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.叙述性综述：酒精性肝炎中的糖皮质激素——益处、副作用及作用机制
J Xenobiot. 2022 Sep 21;12(4):266-288. doi: 10.3390/jox12040019.
5
Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer.糖皮质激素受体二聚化及其在（病理）生理学中的重要性：简介。
Cells. 2022 Feb 15;11(4):683. doi: 10.3390/cells11040683.
6
Current status of glucocorticoid usage in solid organ transplantation.实体器官移植中糖皮质激素的使用现状
World J Transplant. 2021 Nov 18;11(11):443-465. doi: 10.5500/wjt.v11.i11.443.
7
Glucocorticoids as Regulators of Macrophage-Mediated Tissue Homeostasis.糖皮质激素作为调节巨噬细胞介导的组织动态平衡的物质。
Front Immunol. 2021 May 17;12:669891. doi: 10.3389/fimmu.2021.669891. eCollection 2021.
8
Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment.哮喘中的核受体：让经典分子对抗现代疾病
Front Immunol. 2021 Jan 26;11:594433. doi: 10.3389/fimmu.2020.594433. eCollection 2020.
9
Multifaceted Control of GR Signaling and Its Impact on Hepatic Transcriptional Networks and Metabolism.多方位调控 GR 信号及其对肝转录网络和代谢的影响。
Front Endocrinol (Lausanne). 2020 Oct 8;11:572981. doi: 10.3389/fendo.2020.572981. eCollection 2020.
10
Physiological mechanisms underlying children's circannual growth patterns and their contributions to the obesity epidemic in elementary school age children.儿童年轮状生长模式的生理机制及其对小学年龄儿童肥胖流行的影响。
Obes Rev. 2020 Mar;21(3):e12973. doi: 10.1111/obr.12973. Epub 2019 Nov 18.
本文引用的文献
1
Mechanisms of growth hormone (GH) action. Identification of conserved Stat5 binding sites that mediate GH-induced insulin-like growth factor-I gene activation.生长激素（GH）作用机制。介导GH诱导胰岛素样生长因子-I基因激活的保守Stat5结合位点的鉴定。
J Biol Chem. 2003 Dec 19;278(51):51261-6. doi: 10.1074/jbc.M309486200. Epub 2003 Oct 7.
2
STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene.依赖 STAT3 的增强体组装与拆卸：与糖皮质激素受体协同作用以实现α2-巨球蛋白基因转录的完全增加。
Genes Dev. 2003 Oct 15;17(20):2564-77. doi: 10.1101/gad.1135003. Epub 2003 Oct 1.
3
Growth hormone insensitivity associated with a STAT5b mutation.与STAT5b突变相关的生长激素不敏感症
N Engl J Med. 2003 Sep 18;349(12):1139-47. doi: 10.1056/NEJMoa022926.
4
A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro.一种受激素调控的血清因子，可在体外刺激软骨摄取硫酸盐。
J Lab Clin Med. 1957 Jun;49(6):825-36.
5
Circulating levels of IGF-1 directly regulate bone growth and density.胰岛素样生长因子-1（IGF-1）的循环水平直接调节骨骼生长和密度。
J Clin Invest. 2002 Sep;110(6):771-81. doi: 10.1172/JCI15463.
6
Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor.糖皮质激素受体在不结合DNA的情况下对炎症反应的抑制作用。
EMBO J. 2001 Dec 17;20(24):7168-73. doi: 10.1093/emboj/20.24.7168.
7
Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.Stat5a(-/-)5b(-/-)小鼠中由于早期成红细胞存活率降低导致红细胞生成无效。
Blood. 2001 Dec 1;98(12):3261-73. doi: 10.1182/blood.v98.12.3261.
8
Temporal relationship between the sexually dimorphic spontaneous GH secretory profiles and hepatic STAT5 activity.性二态性自发性生长激素分泌模式与肝脏信号转导和转录激活因子5（STAT5）活性之间的时间关系。
Endocrinology. 2001 Nov;142(11):4599-606. doi: 10.1210/endo.142.11.8480.
9
Mammary gland development and lactation are controlled by different glucocorticoid receptor activities.乳腺发育和泌乳受不同糖皮质激素受体活性的控制。
Eur J Endocrinol. 2001 Oct;145(4):519-27. doi: 10.1530/eje.0.1450519.
10
Signaling pathways activated by the growth hormone receptor.生长激素受体激活的信号通路。
Trends Endocrinol Metab. 2001 Aug;12(6):252-7. doi: 10.1016/s1043-2760(01)00423-4.
Zotero 插件