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.
Kong
Sung-Eun
SE
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.
Baxter
Robert C
RC
Delhanty
Patric J D
PJ
D000375:Aging; D000818:Animals; D001667:Binding, Competitive; D001835:Body Weight; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D005215:Fasting; D005502:Food; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000737:chemistry; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics
D002352:Carrier Proteins; D006023:Glycoproteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I