The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown

The metabolic response to fasting involves a series of hormonal and metabol ic adaptations leading to protein conservation. An increase in the serum le vel of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principa l mediator of protein conservation during fasting and to assess the underly ing mechanisms. Eight normal subjects were examined on four occasions: 1) i n the basal postabsorptive state (basal), 2) after 40 h of fasting (fast), 3) after 40 h of fasting with somatostatin suppression of GH (fast-GH), and 4) after 40 h of fasting with suppression of GH and exogenous GH replaceme nt (fast+GH). The two somatostatin experiments mere identical in terms of h ormone replacement (except for GH), meaning that somatostatin, insulin, glu cagon and GH were administered for 28 h; during the last 4 h, substrate met abolism was investigated. Compared with the GH administration protocol, IGF -I and free IGF-I decreased 35 and 70%, respectively, during fasting withou t GH. Urinary urea excretion and serum urea increased when participants fas ted without GH (urea excretion: basal 392 +/- 44, fast 440 +/- 32, fast-GH 609 +/- 76, and fast+GH 408 +/- 36 mmo1/24 h, P < 0.05; serum urea: basal 4 .6 +/- 0.1, fast 6.2 +/- 0.1, fast-GH 7.0 +/- 0.2, and fast+GH 4.3 +/- 0.2 mmol/l, P < 0.01). There was a net release of phenylalanine across the fore arm, and the negative phenylalanine balance was higher during fasting with GH suppression (balance: basal 9 +/- 3, fast 15 +/- 6, fast-GH 17 +/- 4, an d fast+GH 11 +/- 5 nmol/min, P < 0.05). Muscle-protein breakdown was increa sed among participants who fasted without GH (phenylalanine rate of appeara nce: basal 17 +/- 4, fast 26 +/- 9, fast-GH 33 +/- 7, fast+GH 25 +/- 6 nmol /min, P < 0.05). Levels of free fatty acids and oxidation of lipid decrease d during fasting without GH (P < 0.01). In summary, we find that suppressio n of GH during fasting leads to a 50% increase in urea-nitrogen excretion, together with an increased net release and appearance rate of phenylalanine across the forearm. These results demonstrate that GH-possibly by maintena nce of circulating concentrations of free IGF-I-is a decisive component of protein conservation during fasting and provide evidence that the underlyin g mechanism involves a decrease in muscle protein breakdown.