RESUMO
BACKGROUND: Adjuvant growth hormone is advocated for treating the catabolism of prolonged sepsis not corrected by parenteral nutrition alone. METHODS: An open study was performed in which eight patients whose postabsorptive resting energy expenditure was persistently elevated by a mean of 19% as a result of continuing sepsis were randomized to receive 0.03 or 0.06 mg/kg recombinant human growth hormone (rhGH) each evening for 7 days adjuvant to total parenteral nutrition. Plasma concentrations of growth hormone, insulin, insulin-like growth factors 1 and 2 (IGF-1 and -2) and their binding proteins IGFBP-1 and -3 were measured before and after rhGH, and their relationship with rates of whole-body protein turnover was determined in the morning in the postabsorptive state by using L-[1-13C]leucine. RESULTS AND CONCLUSIONS: Before rhGH, the patients were hyperinsulinemic (mean, 44.4 mU/L) but had growth hormone levels within the normal range (< 10 mU/L). After the seventh dose of rhGH, nocturnal growth hormone concentrations rose to a mean of 35.3 +/- 26.1 and 61.3 +/- 21.05 mU/L for the low and higher dose groups, respectively. Morning IGF-1 concentrations showed a small increase during treatment, rising from a mean of 241.3 +/- 99.0 to 301.7 +/- 167.3 ng/mL for the low-dose group and from 214.5 +/- 74.6 to 294.1 +/- 116.9 ng/mL for the higher-dose group. IGF-2 increased slightly by 89 +/- 39 and 75 +/- 49 ng/mL for the low and higher doses, respectively. IGFBP-1 and -3 and insulin did not change. The balance between nitrogen input and urinary urea nitrogen increased after rhGH by a mean of 5.3 g/d with no differences between the two dosage groups (4.74 +/- 1.56 g/d for the higher dose, 5.94 +/- 3.70 g/d for the lower). No significant changes were observed in whole-body protein turnover after a 1-week course of rhGH.
Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Nutrição Parenteral Total , Sepse/sangue , Sepse/terapia , Adulto , Idoso , Ritmo Circadiano , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
This study was designed to investigate the feedback loop between insulin-like growth factor-I (IGF-I) and IGF-II and the hypothalamic hormones growth hormone-releasing hormone (GHRH) and somatostatin (SS) using an in vitro rat hypothalamic model. IGF-I and, to lesser extent, IGF-II, both activate type 1 IGF receptors, while type 2 receptors are activated by IGF-II alone. IGF-I, IGF-II, their various specific analogues (Des[1-3]IGF-I, [Arg54/Arg55]IGF-II and [Leu27]IGF-II), insulin and the type 2 receptor antagonist beta-galactosidase were used on their own or in combination to study their effect on GHRH and SS release. Our results suggest that the simultaneous activation of type 1 and type 2 IGF receptors is needed for the negative feedback effect of IGFs on GHRH release in this in vitro system, in agreement with earlier findings in vivo. Somatostatin was not altered by any combination of peptides.