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Growth hormone (GH) action is primarily mediated by insulin-like growth factor I (IGF-I), although both growth factors show tissue-selective effects. We investigated the effects of GH, IGF-I, and GH plus IGF-I on jejunal growth and function in rats maintained with total parenteral nutrition (TPN) and given recombinant human GH (rhGH) (400 micrograms/day sc, twice daily) and/or rhIGF-I (800 micrograms/day in TPN solution) for 5 days. Administration of GH or IGF-I alone produced similar increases in serum IGF-I levels and body weight; GH plus IGF-I further increased these parameters. TPN reduced mucosal mass, protein and DNA content, villus height, crypt depth, and enterocyte migration rate. IGF-I or GH plus IGF-I produced equivalent increases in all intestinal growth parameters; GH alone had no effect. GH, IGF-I, or GH plus IGF-I reduced TPN-induced increases in sucrase-specific activity. IGF-I, but not GH, attenuated TPN-induced increases in tissue conductance and carbachol-stimulated ion secretion. In contrast to IGF-I, GH does not stimulate intestinal growth during TPN and has less effect on normalizing TPN-induced changes in epithelial function.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) selectively increase tissue mass. We compared the fractional rate of protein synthesis (Ks in skeletal muscle, jejunal mucosa and muscularis, and liver to investigate the differential effects of GH and IGF-I on tissue protein synthesis. Surgically stressed rats were maintained with hypocaloric total parenteral nutrition (TPN) and given recombinant human (rh) GH (rhGH), rhIGF-I, rhGH + rhIGF-I (800 or 800 + 800 micrograms/day, respectively), or TPN alone. After 3 days, a flooding dose of valine (800 mumol with 5.56 MBq L-[3,4-3H]valine) was administered, and rats were killed 20 min later. Body weight gain, nitrogen retention, and serum IGF-I concentrations confirmed that GH plus IGF-I additively increased anabolism. Serum insulin concentrations were significantly increased by GH and decreased by IGF-I. GH significantly increased Ks in skeletal muscle and jejunal muscularis, IGF-I significantly increased Ks in jejunal mucosa and muscularis, and neither GH nor IGF-I altered Ks in liver. GH and IGF-I differentially increase tissue protein synthesis in vivo.

The effect of a standard surgical stress and subsequent total parenteral nutrition (TPN) treatment on systemic acid-base balance was assessed in four groups of rats: TPN controls, TPN coinfused with recombinant human insulin-like growth factor I (rhIGF-I, 800 micrograms/day), TPN with recombinant human growth hormone (rhGH, 800 micrograms in two divided daily sc doses), and combined rhGH plus rhIGF-I (800 + 800 micrograms/day). After the 6-day time course, TPN controls exhibited a systemic metabolic acidosis (HCO3- = 20.4 +/- 0.4 mM) and lost 7 g body wt/6 days. Either growth factor ameliorated the acidosis (rhGH = 22.6 +/- 0.6 and IGF-I = 22.0 +/- 0.5 mM) and promoted weight gain (11 +/- 2 and 10 +/- 3 g/6 days, respectively). Combined growth factor treatment, rhGH+rhIGF-I, restored acid-base balance (HCO3- = 24.7 +/- 0.6 mM) and exhibited an additive effect on weight gain (25 +/- 3 g/6 days). Ammonium and sulfate excretion as indexes of renal acid excretion and systemic sulfuric acid production, respectively, were highest in the TPN control, Growth factors alone reduced sulfuric acid production, whereas combined growth factor treatment reduced acid production and eliminated acid excretion despite elevated renal glutaminase activity. However, renal cortical glutamate content was elevated in the combined growth factor treatment (10.6 +/- 0.7 vs. 7.3 +/- 0.5 rhGH+rhIGF-1 vs. TPN, P < 0.05), consistent with repression of the elevated glutaminase activity. These findings point to an important role for acid-base homeostasis in the anabolic response and are consonant with an additive effect of growth factors, rhGH+rhIGF-I, in correcting the metabolic acidosis associated with surgical stress.

We compared the effects of recombinant human insulin-like growth factor I [rhIGF-I, 800 micrograms/day, coinfused with total parenteral nutrition (TPN)], growth hormone (rhGH, 800 micrograms/day, subcutaneous injection twice daily), and simultaneous treatment with rhIGF-I and rhGH (800 + 800 micrograms/day) in rats subjected to surgical stress and maintained with TPN. Weight gain induced by IGF-I plus GH was double that shown by IGF-I or GH alone. Although weight gain was similar with IGF-I or GH, IGF-I selectively increased heart, kidney, thymus, spleen, and small intestine mass, whereas GH selectively increased gastrocnemius muscle mass. IGF-I and/or GH increased carcass protein and water while decreasing fat. Serum total and free IGF-I levels were highest with IGF-I plus GH. Serum rat GH levels were reduced with IGF-I and/or GH. IGF-I given with GH reversed the GH-induced increase in serum insulin. In summary, IGF-I and GH show tissue-specific anabolic effects, and simultaneous treatment with IGF-I plus GH additively increases anabolism during TPN.