Kong Sung-Eun, Baxter Robert C, Delhanty Patric J D
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.
Endocrinology. 2002 Dec;143(12):4505-12. doi: 10.1210/en.2002-220527.
The GH-dependent, hepatocyte-derived acid-labile subunit (ALS) regulates IGF release from the serum by forming ternary complexes containing IGF binding protein (IGFBP)-3 or IGFBP-5. Malnutrition suppresses ALS and IGF-I expression in a development-dependent manner. Our aim was to investigate whether the effect of feeding following fasting was similarly age dependent. We fasted juvenile and adult rats for 48 h and then refed them, collecting serum and liver tissue at 8, 24, and 48 h. These were compared with rats before fasting (0 h controls) and animals fed throughout the study (free-fed controls). During fasting, serum ALS fell to 25 +/- 5.3% of 0 h controls in juveniles but only 56 +/- 6% in adults. Within 24 h of refeeding, ALS in juveniles had returned to 0 h control levels, and by 48 h to free-fed levels, whereas there was no significant refeeding response in adults during this period. Circulating IGF-I and IGFBP-5 showed similar age-dependent responses to refeeding, rising significantly faster in juveniles. IGFBP-3 did not show this response. Furthermore, hepatic ALS and IGF-I mRNA showed no age-differential response to fasting and refeeding, suggesting posttranscriptional regulation. Neither regulation of hepatic GH receptor nor ALS clearance rates could explain the age-dependent effect. We hypothesize that development-dependent regulation of ALS and IGF-I during refeeding may involve a posttranscriptional hepatic response that is not GH dependent.
生长激素（GH）依赖的、肝细胞衍生的酸不稳定亚基（ALS）通过形成包含胰岛素样生长因子结合蛋白（IGFBP）-3或IGFBP-5的三元复合物来调节血清中IGF的释放。营养不良以发育依赖的方式抑制ALS和IGF-I的表达。我们的目的是研究禁食后进食的影响是否同样依赖年龄。我们将幼年和成年大鼠禁食48小时，然后再喂食它们，在8小时、24小时和48小时收集血清和肝脏组织。将这些与禁食前的大鼠（0小时对照组）和整个研究期间喂食的动物（自由进食对照组）进行比较。在禁食期间，幼年大鼠血清ALS降至0小时对照组的25±5.3%，而成年大鼠仅降至56±6%。再喂食24小时内，幼年大鼠的ALS恢复到0小时对照组水平，到48小时恢复到自由进食水平，而在此期间成年大鼠没有明显的再喂食反应。循环中的IGF-I和IGFBP-5对再喂食表现出类似的年龄依赖性反应，在幼年大鼠中上升明显更快。IGFBP-3没有表现出这种反应。此外，肝脏ALS和IGF-I mRNA对禁食和再喂食没有年龄差异反应表明存在转录后调节。肝脏GH受体的调节或ALS清除率均不能解释这种年龄依赖性效应。我们推测，再喂食期间ALS和IGF-I的发育依赖性调节可能涉及一种不依赖GH的肝脏转录后反应。
