EFFECT OF METABOLIC-ACIDOSIS ON THE EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR AND GROWTH-HORMONE RECEPTOR

To further our understanding of the growth failure in metabolic acidos is, we examined the insulin-like growth factor (IGF-I and IGF-II), the IGF binding protein-3 (IGFBP-3), and the hepatic IGF mRNA and growth hormone receptor mRNA in control, pair-fed and acidotic rats. The rats in the last group were made acidotic by using ammonium chloride (1.5% ) as their sole fluid intake for eight days. Metabolic acidosis was co nfirmed by a blood pH of 7.11 +/- 0.10 (mean +/- SD). The mean startin g weights for all rats were 167.1 +/- 3.4 grams. Growth impairment was observed in the acidotic rats after one week of ammonium chloride int ake. The body weights of the acidotic rats compared to those of the co ntrol rats were 155.5 +/- 18.9 g versus 222.8 +/- 9.7 g, P < 0.001; th e pair-fed rats weighed 156.8 +/- 19.6 grams. All rats were bled and s acrificed on day 8. Sera and tissue were analyzed with the following r esults: compared to the ad libitum controls, the same IGF-I concentrat ions were significantly decreased in the acidotic animals (P < 0.02) a s well as pair-fed controls (P < 0.005). The serum IGF-II and IGF-bind ing protein-3 concentrations were unchanged by acidosis or food restri ction. The hepatic IGF-I mRNA was significantly reduced by acidosis (P < 0.01) and pair-feeding (P < 0.01). Compared to control, the mean he patic IGF mRNA in acidosis was significantly lower (P < 0.01). However , there was no significant difference between the acidotic and the pai r-fed groups. The growth hormone receptor mRNA was depressed in acidos is (P < 0.02), but the data in the pair-fed group did not differ signi ficantly from that of the control group. We conclude that the growth r etardation of metabolic acidosis is related to significantly decreased values of serum IGF-1, inhibition of hepatic IGF-I gene expression an d hepatic growth hormone receptors mRNA. Reduced nutritional intake ma y be an additional factor in the causal relationships.