Bohlooly-Y M, Bollano E, Mobini R, Soussi B, Tornell J, Omerovic E
AstraZeneca Transgenic and Comparative Genomics Centre, Mölndal, Sweden.
Growth Horm IGF Res. 2005 Apr;15(2):148-55. doi: 10.1016/j.ghir.2004.12.007.
Growth hormone (GH) has important regulatory effects on cardiac morphology and function both during normal development as well as in pathophysiological settings such as myocardial infarction (MI) and congestive heart failure (CHF). In order to investigate in more detail the interaction between GH and sympathetic nervous system (SNS) system we studied the effects of selective cerebral GH overexpression on myocardial content of catecholamines, myocardial and brain energy metabolism as well as on cardiac function during resting and stress conditions in a transgenic mouse model.
Transgenic mice with selective bovine GH overexpression under control of glial fibrillary acidic protein promoter in the brain (GFAP-bGH, n=15) were created and compared to genetically matched non-transgenic mates (Control, n=15). Cardiac morphology and function were evaluated in vivo using transthoracic echocardiography during resting and stress conditions induced pharmacologically by dopamine (D) and isoprotenolol (ISO). Myocardial and brain energy metabolism were evaluated non-invasively using in vivo volume-selective phosphorus magnetic resonance spectroscopy ((31)P MRS). Myocardial content of catecholamines was analyzed by means of HPLC.
Compared to the C animals, the GFAP-bGH mice have showed several differences in the cardiac phenotype. Systolic (fractional shortening) and diastolic function (E/A wave ratio of mitral flow) was disturbed in the GFAP-bGH mice (both p<0.05). During the dopamine stress, there was chronotropic insufficiency in the GFAP-bGH group (p<0.01) while no difference was observed in response to isoprotenolol. Left ventricular dimensions were increased in GFAP-bGH mice (p<0.05). There was a tendency for higher body weight in GFAP-bGH compared to the control group (p=0.06) while no difference was observed in heart weight and brain weight when normalized for body weight. Myocardial content of noradrenaline was lower in the GFAP-bGH group (p<0.05). PCr/ATP ratio was higher (p<0.05) in the brain and lower in the heart (p<0.05) in the GFAP-bGH mice.
Selective cerebral overexpression of GH results in alterations of cardiac function, morphology and metabolism in transgenic mice. Decreased myocardial content of catecholamines in the GFAP-bGH mice suggests central interaction between GH and sympathetic nervous system.
生长激素（GH）在正常发育过程中以及在诸如心肌梗死（MI）和充血性心力衰竭（CHF）等病理生理情况下，对心脏形态和功能具有重要的调节作用。为了更详细地研究GH与交感神经系统（SNS）之间的相互作用，我们在转基因小鼠模型中研究了选择性脑GH过表达对心肌儿茶酚胺含量、心肌和脑能量代谢以及静息和应激状态下心脏功能的影响。
构建了在脑胶质纤维酸性蛋白启动子（GFAP-bGH，n = 15）控制下选择性过表达牛GH的转基因小鼠，并与基因匹配的非转基因小鼠（对照，n = 15）进行比较。在静息状态以及由多巴胺（D）和异丙肾上腺素（ISO）药理学诱导的应激状态下，使用经胸超声心动图在体内评估心脏形态和功能。使用体内容积选择性磷磁共振波谱（（31）P MRS）非侵入性地评估心肌和脑能量代谢。通过高效液相色谱法分析心肌儿茶酚胺含量。
与对照动物相比，GFAP-bGH小鼠在心脏表型上表现出若干差异。GFAP-bGH小鼠的收缩功能（缩短分数）和舒张功能（二尖瓣血流E/A波比值）受到干扰（均p < 0.05）。在多巴胺应激期间，GFAP-bGH组出现变时功能不全（p < 0.01），而对异丙肾上腺素的反应未观察到差异。GFAP-bGH小鼠的左心室尺寸增加（p < 0.05）。与对照组相比，GFAP-bGH小鼠体重有增加趋势（p = 0.06），而以体重标准化后，心脏重量和脑重量未观察到差异。GFAP-bGH组心肌去甲肾上腺素含量较低（p < 0.05）。GFAP-bGH小鼠脑内磷酸肌酸/三磷酸腺苷（PCr/ATP）比值较高（p < 0.05），而心脏中该比值较低（p < 0.05）。
GH在脑内的选择性过表达导致转基因小鼠心脏功能、形态和代谢发生改变。GFAP-bGH小鼠心肌儿茶酚胺含量降低表明GH与交感神经系统之间存在中枢相互作用。
