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 acidosis, 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 confirmed by a blood pH of 7.11 +/- 0.10 (mean +/- SD). The mean starting weights for all rats were 167.1 +/- 3.4 grams. Growth impairment was observed in the acidotic rats after one week of ammonium chloride intake. The body weights of the acidotic rats compared to those of the control rats were 155.5 +/- 18.9 g versus 222.8 +/- 9.7 g, P < 0.001; the pair-fed rats weighed 156.8 +/- 19.6 grams. All rats were bled and sacrificed on day 8. Sera and tissue were analyzed with the following results: compared to the ad libitum controls, the same IGF-I concentrations were significantly decreased in the acidotic animals (P < 0.02) as well as pair-fed controls (P < 0.005). The serum IGF-II and IGF-binding protein-3 concentrations were unchanged by acidosis or food restriction. The hepatic IGF-I mRNA was significantly reduced by acidosis (P < 0.01) and pair-feeding (P < 0.01). Compared to control, the mean hepatic IGF mRNA in acidosis was significantly lower (P < 0.01). However, there was no significant difference between the acidotic and the pair-fed groups.(ABSTRACT TRUNCATED AT 250 WORDS)