Age-Dependent Regulation of the Acid-Labile Subunit in Response to Fasting-Refeeding in Rats

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.