Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake.

ABSTRACT

This study was designed to test the hypothesis that induction of insulin-like growth factor-1 (IGF-1) is reduced in the uremic rat liver, which would help to explain the purported growth hormone resistance noted in uremia. IGF-1 mRNA, in the steady state and after acute induction by two doses of 100 micrograms/100 g body wt recombinant human growth hormone (rhGH), was quantitated by solution hybridization in total liver RNA, extracted by the guanidine thiocyanate/cesium chloride gradient method. Eighteen Sprague-Dawley rats weighing 100 to 102 g were randomly divided into three groups sham-operated control rats (control group); 5/6 nephrectomized rats (uremic group); and sham-operated controls with dietary intake matching that of the uremic rats (pair-fed group). The results showed that the steady state liver IGF-1 mRNA was 1.7 arbitrary densitometry units (ADU) in the uremic animals, and was lower than the value of 3.2 ADU in the control animals (P < 0.05). After the acute administration of rhGH, the liver IGF-1 mRNA of control, uremic and pair-fed groups showed mean increases of 154% (P < 0.05), 124% (not significant, NS) and 117% (NS), respectively. The lack of IGF-1 induction in the uremic group supported the concept of growth hormone resistance in uremia. In addition, a similar lack of induction was observed in the pair-fed group, whose food intake was 65% that of the control animals. This indicated that the lack of IGF-1 induction was at least partially due to the reduced food intake.(ABSTRACT TRUNCATED AT 250 WORDS)