CALORIC RESTRICTION AND EXPRESSION OF LIVER INSULIN-LIKE GROWTH FACTOR-I, GROWTH-HORMONE RECEPTOR AND PITUITARY GROWTH-HORMONE

The relationship between degree and duration of reduced food intake an d the expression of liver insulin-like growth factor-I (IGF-I) and gro wth hormone receptor (GHR) mRNA in relationship to body weight gain wa s examined. The first experiment used 12 adult male Sprague-Dawley rat s fed 60% of food intake of the 12 control rats. On days 10, 15 and 20 , four rats from each group were sacrificed. Liver samples were homoge nized in 4M guanidine thiocyanide and total liver RNA was isolated by cesium chloride gradient centrifugation. Compared to the controls, bod y weight gain of the animals on 60% food intake was significantly lowe r and was correlated with the reduction of liver IGF-I mRNA expressed in arbitrary densitometric units (ADU) [Control: 1.1 +/- .06; rats on 60% food intake at 10 days: 0.9 +/- .08; at 15 days: 0.8 +/- .03 (P < .05) and at 21 days: 0.7 +/- .09 (P < .02)]. The GHR mRNA was not affe cted. In a second experiment, eight rats each were fed 30% and 60% foo d intake of the eight control animals for 5 and 10 days. With 30% food intake, both liver IGF-I and GHR mRNA were significantly reduced as e arly as day 5 and further decreases were evident at day 10. The hepati c growth hormone receptor mRNA showed significant reduction only in th e 30% food intake group. This group of animals did not show any weight gain throughout the experimental period. On the other hand, the pitui tary growth hormone expression was not affected by the experimental co nditions in this study. We conclude that both the duration as well as the severity of food restriction significantly limit the expression of liver IGF-I and GHR.