Luque Raul M, Park Seungjoon, Kineman Rhonda D
Department of Medicine, University of Illinois, Chicago, USA.
Endocrinology. 2007 Jan;148(1):300-9. doi: 10.1210/en.2006-0592. Epub 2006 Oct 12.
To determine whether the severity of the catabolic condition differentially regulates the GH axis, male mice were either fed ad libitum or fasted for 12, 24, and 48 h. Hypothalami, pituitaries, and stomachs were collected for assessment of mRNA levels by quantitative real-time RT-PCR, and blood collected for measurement of plasma hormone and metabolite levels by commercial assay kits. Overnight (12 h) fasting resulted in a significant suppression of circulating glucose, insulin, IGF-I, and leptin levels and an increase in corticosterone, free fatty acids, and n-octanoyl ghrelin levels, and these directional changes were maintained at the 24- and 48-h time points. Fasting (24 h) also increased circulating GH levels, which was associated with an increase in pituitary mRNA levels for GHRH receptor and ghrelin receptor and a decrease in mRNA levels for somatostatin (SST) receptor (SSTR) subtypes, SSTR2, SSTR3, and SSTR5, where the changes in ghrelin receptor and SSTR expression persisted after 48 h fasting. Hypothalamic SST mRNA levels were not altered by fasting, whereas there was a transient rise in stomach SST mRNA levels 24 h after food withdrawal. In contrast, there was a biphasic effect of fasting on GHRH expression. GHRH mRNA levels were significantly elevated at 12 and 24 h but fell to approximately 50% of fed controls 48 h after food withdrawal. A sequential rise in hypothalamic neuropeptide Y (NPY) and CRH mRNA levels preceded the fall in GHRH expression, where fasting-induced changes in CRH and GHRH mRNA levels were not observed in 48-h-fasted NPY knockout mice. These observations, in light of previous reports showing both NPY and CRH can inhibit GHRH expression and GH release, suggest that these neuronal systems may work in concert to control the ultimate impact of fasting on GH axis function.
为了确定分解代谢状态的严重程度是否对生长激素（GH）轴有不同的调节作用，将雄性小鼠分为自由采食组或禁食12、24和48小时组。收集下丘脑、垂体和胃，通过定量实时逆转录聚合酶链反应（RT-PCR）评估mRNA水平，并采集血液，使用商用检测试剂盒测量血浆激素和代谢物水平。过夜（12小时）禁食导致循环葡萄糖、胰岛素、胰岛素样生长因子-I（IGF-I）和瘦素水平显著降低，皮质酮、游离脂肪酸和正辛酰胃泌素水平升高，并且这些方向性变化在24小时和48小时时间点维持不变。禁食（24小时）还会增加循环GH水平，这与垂体中生长激素释放激素（GHRH）受体和胃泌素受体的mRNA水平升高以及生长抑素（SST）受体（SSTR）亚型SSTR2、SSTR3和SSTR5的mRNA水平降低有关，其中胃泌素受体和SSTR表达的变化在禁食48小时后持续存在。禁食并未改变下丘脑SST mRNA水平，而在食物撤除后24小时胃SST mRNA水平有短暂升高。相比之下，禁食对GHRH表达有双相效应。GHRH mRNA水平在12小时和24小时时显著升高，但在食物撤除后48小时降至约为自由采食对照组的50%。下丘脑神经肽Y（NPY）和促肾上腺皮质激素释放激素（CRH）mRNA水平在GHRH表达下降之前依次升高，在禁食48小时的NPY基因敲除小鼠中未观察到禁食诱导的CRH和GHRH mRNA水平变化。鉴于之前的报道显示NPY和CRH均可抑制GHRH表达和GH释放，这些观察结果表明这些神经元系统可能协同作用以控制禁食对GH轴功能的最终影响。
