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不同的 GH 给药方式会影响雄性大鼠大脑中的基因表达。

Different modes of GH administration influence gene expression in the male rat brain.

机构信息

Laboratory of Experimental EndocrinologyDepartment of Internal Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Blå Stråket 5, SE-413 45 Gothenburg, SwedenDepartment for Public Health and Community MedicineThe Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenAstraZeneca R&DSE-431 83 Mölndal, Gothenburg, SwedenInstitute for Neuroscience and PhysiologyThe Sahlgrenska Academy, Center for Brain Repair and RehabilitationDepartment of Primary Health CareInstitute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Laboratory of Experimental EndocrinologyDepartment of Internal Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Blå Stråket 5, SE-413 45 Gothenburg, SwedenDepartment for Public Health and Community MedicineThe Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenAstraZeneca R&DSE-431 83 Mölndal, Gothenburg, SwedenInstitute for Neuroscience and PhysiologyThe Sahlgrenska Academy, Center for Brain Repair and RehabilitationDepartment of Primary Health CareInstitute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenLaboratory of Experimental EndocrinologyDepartment of Internal Medicine, The Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Blå Stråket 5, SE-413 45 Gothenburg, SwedenDepartment for Public Health and Community MedicineThe Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenAstraZeneca R&DSE-431 83 Mölndal, Gothenburg, SwedenInstitute for Neuroscience and PhysiologyThe Sahlgrenska Academy, Center for Brain Repair and RehabilitationDepartment of Primary Health CareInstitute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

J Endocrinol. 2014 Aug;222(2):181-90. doi: 10.1530/JOE-14-0223. Epub 2014 May 28.

DOI:10.1530/JOE-14-0223
PMID:24872576
Abstract

The endogenous secretion pattern in males of GH is episodic in rats and in humans, whereas GH administration is usually even. Different types of GH administration have different effects on body mass, longitudinal bone growth, and liver metabolism in rodents, whereas possible effects on brain plasticity have not been investigated. In this study, GH was administered as a continuous infusion or as two daily injections in hypophysectomized male rats. Thirteen transcripts previously known to respond to GH in the hippocampus and parietal cortex (cortex) were assessed by RT-PCR. To investigate the effects of type of GH administration on several transcripts with different variations, and categories of transcripts (neuron-, glia-, and GH-related), a mixed model analysis was applied. Accordingly, GH injections increased overall transcript abundance more than GH infusions (21% in the hippocampus, P<0.001 and 10% in the cortex, P=0.09). Specifically, GH infusions and injections robustly increased neuronal hemoglobin beta (Hbb) expression significantly (1.8- to 3.6-fold), and GH injections were more effective than GH infusions in increasing Hbb in the cortex (41%, P=0.02), whereas a 23% difference in the hippocampus was not significant. Also cortical connexin 43 was higher in the group with GH injections than in those with GH infusions (26%, P<0.007). Also, there were differences between GH injections and infusions in GH-related transcripts of the cortex (23%, P=0.04) and glia-related transcripts of the hippocampus (15%, P=0.02). Thus, with the exception of Hbb there is a moderate difference in responsiveness to different modes of GH administration.

摘要

男性 GH 的内源性分泌模式在大鼠和人类中呈间歇性,而 GH 给药通常是均匀的。不同类型的 GH 给药对啮齿动物的体重、纵向骨生长和肝脏代谢有不同的影响,而对大脑可塑性的可能影响尚未得到研究。在这项研究中,GH 被连续输注或每天两次注射给予去垂体的雄性大鼠。通过 RT-PCR 评估了先前已知在海马体和顶叶皮层(皮层)中对 GH 有反应的 13 个转录本。为了研究不同类型的 GH 给药对几种具有不同变化和转录本类别(神经元、神经胶质和 GH 相关)的转录本的影响,应用了混合模型分析。相应地,GH 注射比 GH 输注更能增加整体转录本丰度(海马体增加 21%,P<0.001,皮层增加 10%,P=0.09)。具体而言,GH 输注和注射均能显著增加神经元血红蛋白 beta(Hbb)的表达(增加 1.8-3.6 倍),且 GH 注射在皮层中增加 Hbb 的效果优于 GH 输注(增加 41%,P=0.02),而在海马体中增加 23%差异不显著。此外,与 GH 输注组相比,GH 注射组的皮质连接蛋白 43 更高(增加 26%,P<0.007)。此外,皮质的 GH 相关转录本和海马体的神经胶质相关转录本在 GH 注射和输注之间也存在差异(皮质增加 23%,P=0.04;海马体增加 15%,P=0.02)。因此,除了 Hbb 之外,对不同模式的 GH 给药的反应存在中等差异。

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