ABSTRACT
Suppressor of cytokine sigaling (SOCS) genes encode a family of protein recently identified as negative feedback inhibitors of signaling by eytokine receptors. We have previously shown that endotoxin markedly stimulates SOCS gene expression in rat liver, that correlates with observed resistance to growth hormone-signaling during endotoxemia. The objective of this study was to determine the expression of SOCS genes in state of fasting that have been shown to cause altered responses in pro-inflammatory cytokines and anzbolic hormones. Male Sprague-Dawley rats (～200g) were fasted for 1, 2 or 3 days, or refed for 3 days following a 3-day period of fasting. Liver and muscle mRNAs were determinedby Northern blotting using specific rat cDNA probes cloned in our laboratory. In liver, after a l-day lag period, there was a progressive 2-fold increase in SOCS-3 and 75% decrease in SOCS-2 mRNA afte 2 and 3 of fasting. Both SOCS mRNAs were normalized by 3 days of refeeding. There was no measurable changes in tyrosine phosphorylation of STAT1, STAT3, STAT5a or STAT5b, nor activation of MAP kinases including ERK 1/2, p38, and JUNK 1/2 in liver by 3 days of fasting. In muscle, there was a similar 75% decrease in SOCS-2 mRNA, but no change in SOCS-3 mRNA following 3 days of fasting. These data suggest that malnutrition regulates SOCS-2 and SOCS-3 in a different way, and this regulation is tissue specific. The changes of SOCS mRANs are independent of measurable phosphoryiation of multiple STATs and activation of MAP kinasea. The altered SOCS expressions during fasting may explain the changes of biological effects of multiple cytokines and anabolie hormones in malnutrition states.