The Protein-Retaining Effects of Growth Hormone During Fasting Involve Inhibition of Muscle-Protein Breakdown

Helene Nørrelund, K. Sreekumaran Nair, Jens Otto Lunde Jørgensen, Jens Sandahl Christiansen, and Niels Møller

From Medical Department M (Endocrinology and Diabetes) (H.N., J.O.L.J., J.S.C., N.M.), Aarhus Kommunehospital, Aarhus, Denmark; and the Endocrinology Division (K.S.N.), Mayo Clinic, Rochester, Minnesota.

Address correspondence and reprint requests to: Helene Nørrelund, Medical Department M, Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark. E-mail: helenenorrelund@dadlnet.dk .

The metabolic response to fasting involves a series of hormonal and metabolic adaptations leading to protein conservation. An increase in the serum level of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principal mediator of protein conservation during fasting and to assess the underlying mechanisms. Eight normal subjects were examined on four occasions: 1) in 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 replacement (fast+GH). The two somatostatin experiments were identical in terms of hormone replacement (except for GH), meaning that somatostatin, insulin, glucagon and GH were administered for 28 h; during the last 4 h, substrate metabolism was investigated. Compared with the GH administration protocol, IGF-I and free IGF-I decreased 35 and 70%, respectively, during fasting without GH. Urinary urea excretion and serum urea increased when participants fasted without GH (urea excretion: basal 392 ± 44, fast 440 ± 32, fast-GH 609 ± 76, and fast+GH 408 ± 36 mmol/24 h, P < style="font-style: italic;">In summary, we find that suppression 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 maintenance of circulating concentrations of free IGF-I—is a decisive component of protein conservation during fasting and provide evidence that the underlying mechanism involves a decrease in muscle protein breakdown.