Ogawa E, Breier B H, Bauer M K, Gallaher B W, Grant P A, Walton P E, Owens J A, Gluckman P D
Research Center for Developmental Medicine and Biology, University of Auckland School of Medicine, New Zealand.
Endocrinology. 1996 Apr;137(4):1242-8. doi: 10.1210/endo.137.4.8625895.
The effects of recombinant bovine GH (rbGH) treatment on the insulin-like growth factor (IGF) axis and protein metabolism during fasting induced metabolic stress were evaluated in young lambs. To explore whether rbGH pretreatment alone might offer a degree of protection against nutritional stress, we compared the effects of rbGH given only before or during the fasting-induced metabolic stress with that given over the whole period. The animals were fed ad libitum for 5 days (well fed phase) and then fasted for 70 h (fasted phase). The rbGH was administered during either the well fed and the fasted phase (G-G), only during the well fed phase (G-S), or only during the fasted phase (S-G), and the effects were compared with those of saline treatment throughout both phases (S-S; n = 7/group). The rate of net protein catabolism, analyzed on the final day of the study, was reduced (P < 0.001) to a similar degree in all rbGH-treated groups compared with that in the S-S group. rbGH pretreatment was as effective as rbGH administered during the catabolic phase. Plasma IGF-I was increased (P < 0.001) in the well fed phase by rbGH treatment and decreased in the fasted phase in all groups. The rbGH treatment during the fasted phase resulted in a smaller fall in plasma IGF-I levels than saline treatment (P < 0.05, G-G vs G-S and S-G vs. S-S), but no difference was observed in the specific binding of [125I]ovine GH to the hepatic membranes from animals of the different groups. There was a negative correlation between net protein catabolism and plasma IGF-I levels (r = -0.48; P < 0.01) and specific binding of [125I]ovine GH to hepatic membranes (r = -0.56; P < 0.001). Plasma IGF-II levels were decreased by rbGH treatment during the well fed phase, but the responses to treatment during the fasted phase were variable, suggesting that plasma IGF-II is regulated in a different manner than plasma IGF-I. The fasting-induced fall (P < 0.05) in plasma concentrations of IGF-binding protein (IGFBP)-3 was reduced with rbGH treatment, and plasma concentrations IGFBP-2 were altered in an inverse manner. This study suggests that fasting-induced GH resistance can be alleviated by rbGH treatment independent of whether treatment is commenced before or after the onset of catabolic stress. Our observation of prolonged anticatabolic action of prophylactic rbGH treatment supports the proposal that prophylactic use of GH may reduce the degree of catabolism associated with subsequent interventions and, thus, improve clinical outcome.
在幼龄羔羊中评估了重组牛生长激素（rbGH）处理对禁食诱导的代谢应激期间胰岛素样生长因子（IGF）轴和蛋白质代谢的影响。为了探究单独的rbGH预处理是否能提供一定程度的抗营养应激保护，我们比较了仅在禁食诱导的代谢应激之前或期间给予rbGH与在整个期间给予rbGH的效果。动物自由采食5天（饱食期），然后禁食70小时（禁食期）。rbGH在饱食期和禁食期（G-G）、仅在饱食期（G-S）或仅在禁食期（S-G）给药，并将效果与两个阶段均给予生理盐水处理的组（S-S；每组n = 7）进行比较。在研究的最后一天分析的净蛋白质分解代谢率，与S-S组相比，所有接受rbGH处理的组均降低（P < 0.001）至相似程度。rbGH预处理与在分解代谢期给予rbGH一样有效。在饱食期，rbGH处理使血浆IGF-I升高（P < 0.001），而在禁食期所有组的血浆IGF-I均降低。禁食期给予rbGH处理导致血浆IGF-I水平的下降幅度小于生理盐水处理（P < 0.05，G-G组与G-S组以及S-G组与S-S组相比），但不同组动物的肝细胞膜上[125I]羊生长激素的特异性结合未观察到差异。净蛋白质分解代谢与血浆IGF-I水平之间呈负相关（r = -0.48；P < 0.01），与[125I]羊生长激素与肝细胞膜的特异性结合也呈负相关（r = -0.56；P < 0.001）。在饱食期，rbGH处理使血浆IGF-II水平降低，但禁食期对处理的反应各不相同，这表明血浆IGF-II的调节方式与血浆IGF-I不同。rbGH处理可减轻禁食诱导的血浆胰岛素样生长因子结合蛋白（IGFBP）-3浓度下降（P < 0.05），而血浆IGFBP-2浓度则呈相反变化。本研究表明，无论在分解代谢应激开始之前还是之后开始治疗，rbGH处理均可减轻禁食诱导的生长激素抵抗。我们观察到预防性rbGH处理具有延长的抗分解代谢作用，这支持了预防性使用生长激素可能降低与后续干预相关的分解代谢程度从而改善临床结局的观点。
