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禁食调节雌性小鼠乳腺中的生长激素/胰岛素样生长因子-I轴及其调节系统:内源性可体松的影响。

Fasting modulates GH/IGF-I axis and its regulatory systems in the mammary gland of female mice: Influence of endogenous cortistatin.

作者信息

Villa-Osaba Alicia, Gahete Manuel D, Cordoba-Chacon José, de Lecea Luis, Castaño Justo P, Luque Raúl M

机构信息

Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Spain; CIBERobn, Córdoba, Spain; ceiA3, Córdoba, Spain.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.

出版信息

Mol Cell Endocrinol. 2016 Oct 15;434:14-24. doi: 10.1016/j.mce.2016.06.014. Epub 2016 Jun 9.

DOI:10.1016/j.mce.2016.06.014
PMID:27291340
Abstract

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are essential factors in mammary-gland (MG) development and are altered during fasting. However, no studies have investigated the alterations in the expression of GH/IGF-I and its regulatory systems (somatostatin/cortistatin and ghrelin) in MG during fasting. Therefore, this study was aimed at characterizing the regulation of GH/IGF-I/somatostatin/cortistatin/ghrelin-systems expression in MG of fasted female-mice (compared to fed-controls) and the influence of endogenous-cortistatin (using cortistatin-knockouts). Fasting decreased IGF-I while increased IGF-I/Insulin-receptors expression in MGs. Fasting provoked an increase in GH expression that might be associated to enhanced ghrelin-variants/ghrelin-O-acyl-transferase enzyme expression, while an upregulation of somatostatin-receptors was observed. However, cortistatin-knockouts mice showed a decrease in GH and somatostatin receptor-subtypes expression. Altogether, we demonstrate that GH/IGF-I, somatostatin/cortistatin and ghrelin systems expression is altered in MG during fasting, suggesting a relevant role in coordinating its response to metabolic stress, wherein endogenous cortistatin might be essential for an appropriate response.

摘要

生长激素(GH)和胰岛素样生长因子-I(IGF-I)是乳腺(MG)发育的关键因素,且在禁食期间会发生变化。然而,尚无研究探讨禁食期间MG中GH/IGF-I及其调节系统(生长抑素/皮质抑素和胃饥饿素)表达的改变。因此,本研究旨在表征禁食雌性小鼠(与喂食对照相比)MG中GH/IGF-I/生长抑素/皮质抑素/胃饥饿素系统表达的调节以及内源性皮质抑素(使用皮质抑素基因敲除小鼠)的影响。禁食使MG中的IGF-I减少,而IGF-I/胰岛素受体表达增加。禁食引发GH表达增加,这可能与胃饥饿素变体/胃饥饿素-O-酰基转移酶表达增强有关,同时观察到生长抑素受体上调。然而,皮质抑素基因敲除小鼠的GH和生长抑素受体亚型表达降低。总之,我们证明禁食期间MG中GH/IGF-I、生长抑素/皮质抑素和胃饥饿素系统表达发生改变,表明其在协调对代谢应激的反应中具有重要作用,其中内源性皮质抑素可能是适当反应所必需的。

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