Metabolic acidosis inhibits growth hormone secretion in rats: Mechanism of growth retardation

To test the hypothesis that growth retardation in nonanion gap acidosis may be associated with impairment of growth hormone (GH) secretory patterns, we examined GH secretion in rats made acidotic with ammonium chloride ingestion. Considerable growth retardation was demonstrated in pair-fed and acidotic rats after 1 wk of ammonium chloride ingestion compared with control. With stable metabolic acidosis sustained on the 8th day of experiment, pulsatile secretion of GH was evaluated by blood samples drawn every 10 min for 6 h. Using deconvolution analysis to quantitate in vivo GH secretory rates, we found significant inhibition of pulsatile GH secretion in acidotic rats. Changes in amplitude of GH pulses and mean mass of GH pulses correlated with changes in body weight. These studies showed that chronic metabolic acidosis causes growth impairment, reduced food efficiency, and amplitude-specific inhibition of pulsatile secretion of GH. We propose that this GH axis suppression, whether mediated by decreased nutrients or not, contributes significantly to growth failure in children with renal tubular acidosis. Because a similar degree of inhibition of GH secretion was seen in pair-fed rats, we infer that insufficient calorie intake in metabolic acidosis may contribute to disruption of normal GH secretion patterns. These changes in GH secretion were specific, because acidotic rats were different from pair-fed controls in that they showed no change in either half-life of GH in circulation or in pulse frequency. Such observations offer a rationale for more detailed clinical investigations into the impact of metabolic acidosis on physiological regulation of pulsatile GH secretion in humans.