Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat.
Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat.
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DOI：
10.1677/joe.0.1800369
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发表时间：
2004-03
期刊：
影响因子：
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通讯作者：
Seungjoon Park;Sookjin Sohn;R. Kineman
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文献类型：
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作者：
Seungjoon Park;Sookjin Sohn;R. Kineman
禁食导致成年雄性大鼠下丘脑神经肽Y（NPY）和生长激素释放激素（GHRH）表达的相互变化。据推测，禁食诱导的NPY升高是GHRH下降和随后的GH脉冲释放衰减的原因。禁食也导致循环IGF-I减少，这归因于GH释放减少和外周GH抵抗。尽管禁食大鼠垂体GH输出被抑制，但我们在此报告垂体GHRH受体（GHRH-R）和GH促分泌素受体（GHS-R）mRNA水平增加，而垂体生长抑素受体亚型2（SST 2）和5（SST 5）的表达减少，如通过实时逆转录（RT）-PCR所确定的。垂体受体亚型的表达发生变化，有利于GH的合成和释放，这可能是由于，至少部分是由于GH/IGF-I负反馈下降。为了验证这一假设，我们比较了下丘脑和垂体反应禁食（72小时）在正常雄性大鼠和大鼠孤立GH缺乏症（自发性侏儒大鼠（SDR））。循环GH水平在SDR中检测不到，IGF-I水平低于正常对照的10%。在SDR中，禁食刺激NPY mRNA水平;然而，在禁食正常大鼠中观察到，NPY mRNA水平的上升并不伴随着GHRH mRNA的下降。事实上，GHRH mRNA水平在禁食SDR中矛盾地上升到进食对照的135%。在垂体水平，禁食并没有改变sst 2和sst 5的mRNA水平在SDR，但刺激GHRH-R和GHS-R的表达，分别为165%和149%的美联储控制。这些结果表明，禁食诱导的垂体sst 2和sst 5表达的变化，而不是GHRH-R和GHS-R，是GH/IGF-I依赖性的。此外，这些结果反驳了禁食后观察到的NPY和GHRH表达的负相关代表简单的因果关系的理论，并表明GH直接或间接介导了禁食对下丘脑GHRH表达的影响。
Fasting results in a reciprocal shift in hypothalamic neuropeptide Y (NPY) and GH-releasing hormone (GHRH) expression in the adult male rat. It is hypothesized that the fasting-induced rise in NPY is responsible for the GHRH decline and subsequent attenuation of pulsatile GH release. Fasting also leads to a decrease in circulating IGF-I, attributed to both reduced GH release and peripheral GH resistance. Although pituitary GH output is suppressed in the fasted rat, we report herein that pituitary GHRH receptor (GHRH-R) and GH secretagogue receptor (GHS-R) mRNA levels are increased, while pituitary expression of the somatostatin receptor subtype 2 (sst2) and 5 (sst5) is decreased, as determined by real-time reverse transcription (RT)-PCR. A shift in the expression of pituitary receptor subtypes to favor GH synthesis and release may be due, at least in part, to a decline in GH/IGF-I negative feedback. In order to test this hypothesis, we compared hypothalamic and pituitary response to fasting (72 h) in normal male rats and rats with isolated GH deficiency (spontaneous dwarf rats (SDR)). Circulating GH levels were undetectable in SDR, and IGF-I levels were less than 10% of normal controls. Fasting stimulated NPY mRNA levels in SDR; however, the rise in NPY mRNA levels was not accompanied by a fall in GHRH mRNA, as observed in fasted normal rats. In fact, GHRH mRNA levels paradoxically rose in the fasted SDR to 135% of fed controls. At the pituitary level, fasting did not alter sst2 and sst5 mRNA levels in SDR but did stimulate the expression of GHRH-R and GHS-R to 165% and 149% of fed controls, respectively. These results demonstrate that the fasting-induced changes in pituitary expression of sst2 and sst5, but not GHRH-R and GHS-R, are GH/IGF-I dependent. In addition, these results argue against the theory that the negative association of NPY and GHRH expression observed following fasting represents a simple cause-and-effect relationship and suggest that GH, either directly or indirectly, mediates the effects of fasting on hypothalamic GHRH expression.