Rapid modulation of protein synthesis in normal rats by specific neutralization and replacement of growth hormone.

Since acute treatment with antibodies to rat GH (ArGH) rapidly and specifically neutralizes the activity of circulating rat GH (rGH), the effect of rapid changes in GH status on protein synthesis was examined in diaphragm muscle from normal rats treated acutely with ArGH or control serum via an indwelling iv cannula. The incorporation of tritiated amino acids into muscle protein served as an index of protein synthesis. Rats were treated with serum twice in 3 h; 3 h later, the diaphragm muscle was incubated with [3H]leucine or [3H]phenylalamine. Under these conditions, the basal incorporation of the amino acids into muscle protein was lower after ArGH treatment. In these tissues, the addition of GH (5 micrograms/ml) in vitro restored protein synthesis to control levels within 90 min, whereas tissues from rats treated with control serum were not stimulated by the added GH. In all experiments, neutralization of the biological activity of GH by ArGH was verified by loss of the specific refractory effect of GH in adipose tissue from the same animals. Thus, neutralization of circulating GH by ArGH is accompanied by a reduction in basal protein synthesis in muscle from normal rats; added GH rapidly restores amino acid incorporation to normal levels. These findings suggest that in normal animals, endogenous GH participates in sustaining protein synthesis in muscle and that rapid changes in circulating GH are accompanied by rapid changes in protein synthesis in muscle.