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

Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia

Address all correspondence and requests for reprints to: Dr. P. J. D. Delhanty, Kolling Institute of Medical Research, Royal North Shore Hospital, Pacific Highway, St. Leonards, New South Wales 2065, Australia. E-mail: delhanty{at}med.usyd.edu.au.

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.

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