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生长激素缺乏(lit/lit)小鼠以及过表达牛生长激素(bGH)或bGH拮抗剂的转基因小鼠的垂体和肝脏中生长激素(GH)受体及胰岛素样生长因子-I基因表达的组织特异性调控

Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH-deficient (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH antagonist.

作者信息

Iida Keiji, Del Rincon Juan P, Kim Dong-Sun, Itoh Emina, Nass Ralf, Coschigano Karen T, Kopchick John J, Thorner Michael O

机构信息

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.

出版信息

Endocrinology. 2004 Apr;145(4):1564-70. doi: 10.1210/en.2003-1486. Epub 2004 Jan 15.

DOI:10.1210/en.2003-1486
PMID:14726438
Abstract

GH has diverse biological actions that are mediated by binding to a specific, high-affinity cell surface receptor (GHR). Expression of GHR is tissue specific and a requirement for cellular responsiveness to GH. IGF-I is produced in multiple tissues and regulated in part by GH through GHR. In this study, we evaluated GHR and IGF-I mRNA expression in pituitary gland and compared the levels with those derived from liver of bovine GH transgenic, GH antagonist transgenic, lit/lit mice, and their respective controls using real-time RT-PCR. In liver, both GHR and IGF-I mRNA expressions were regulated in parallel with GH action in all three animal models, and there was a strong correlation between GHR and IGF-I mRNA levels. In the pituitary gland, increased expression of IGF-I mRNA in the pituitary of bovine GH transgenic mice was observed, whereas IGF-I expression in GH antagonist transgenic or lit/lit mice was similar to that observed in control animals. There were no differences of GHR mRNA levels in pituitary gland of any groups we examined. There was also no correlation between GHR and IGF-I mRNA levels in any group in the pituitary gland. In conclusion, we found that hepatic GHR and IGF-I mRNA levels were strongly correlated with each other in chronic GH excess or deficient state, and that regulation and correlation between local GHR and IGF-I mRNA levels induced by GH is different between liver and pituitary gland.

摘要

生长激素(GH)具有多种生物学作用,这些作用是通过与特定的、高亲和力的细胞表面受体(GHR)结合来介导的。GHR的表达具有组织特异性,是细胞对GH产生反应的必要条件。胰岛素样生长因子-I(IGF-I)在多种组织中产生,并部分受GH通过GHR的调节。在本研究中,我们使用实时逆转录聚合酶链反应(RT-PCR)评估了垂体中GHR和IGF-I mRNA的表达,并将其水平与牛GH转基因小鼠、GH拮抗剂转基因小鼠、lit/lit小鼠及其各自对照的肝脏中相应水平进行了比较。在肝脏中,在所有三种动物模型中,GHR和IGF-I mRNA的表达均与GH作用平行调节,并且GHR和IGF-I mRNA水平之间存在很强的相关性。在垂体中,观察到牛GH转基因小鼠垂体中IGF-I mRNA表达增加,而GH拮抗剂转基因小鼠或lit/lit小鼠中的IGF-I表达与对照动物中观察到的相似。我们检查的任何组的垂体中GHR mRNA水平均无差异。垂体中任何组的GHR和IGF-I mRNA水平之间也无相关性。总之,我们发现,在慢性GH过量或缺乏状态下,肝脏中的GHR和IGF-I mRNA水平彼此密切相关,并且GH诱导的局部GHR和IGF-I mRNA水平之间的调节和相关性在肝脏和垂体之间是不同的。

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