Time course of the response to recombinant growth hormone in acidotic mice.

Long-term administration of recombinant growth hormone (GH) increases growth, despite persistent acidosis, in mice with carbonic anhydrase II deficiency (CAD). In contrast, short-term administration of GH to acidotic rats fails to improve growth. To determine the factors affecting the rate of growth response to GH in acidosis, we analyzed serial measurements obtained during a randomized trial of GH in CAD mice and healthy controls. Administration of GH increased standardized growth progressively up to 5-9 weeks. These data suggest that assessment of the response to GH in rodents requires prolonged administration.

Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis.

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from approximately 5 to approximately 12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.