Briard N, Guillaume V, Frachebois C, Rico-Gomez M, Sauze N, Oliver C, Dutour A
Laboratoire de Neuroendocrinologie Experimentale, INSERM U297, Institut Fédératif Jean Roche, Marseille, France.
Endocrinology. 1998 Jun;139(6):2662-9. doi: 10.1210/endo.139.6.6072.
Endotoxin has been shown to stimulate GH secretion in human and sheep. However, changes in hypothalamic neurohormones involved in the GH regulation by endotoxin have never been studied in vivo. In sheep it is possible to collect hypophysial portal blood (HPB) and quantify GH-releasing hormone (GHRH) and somatostatin (SRIH) secretion under physiological conditions. The purpose of this study was to determine the effect of an acute i.v. endotoxin administration on the secretion of these peptides in sheep. Endotoxin induced a sustained increase of GH (x6.2 +/- 1.3) in intact rams. This stimulation was delayed and less marked when compared with the hypothalamic-pituitary-adrenal axis. Surprisingly, the GH increase was associated with an important rise of jugular (x10.6 +/- 2.4) and portal (x7.9 +/- 3) SRIH levels, without a significant GHRH increase. To determine if the portal SRIH increase was a consequence of an increased short feedback of GH, we studied GH response to endotoxin after a previous GHRH injection to deplete the pituitary pools of GH. In that case, despite the absence of increase of GH after endotoxin treatment, SRIH levels was markedly increased. For the first time we have observed an experimental situation in sheep with a simultaneous and closed amplitude increase in jugular and portal SRIH. The source of jugular SRIH is likely the gastrointestinal tract and the increased jugular SRIH release in systemic circulation might be in part responsible for the increase of hypophysial portal SRIH. Ultimately our results show that endotoxin induced a complex reaction at multiple levels with a specific increase in both portal and peripheral SRIH levels. The surprising association of a lack of change in GHRH release and an increased secretion of SRIH with the increase of GH suggests that the effect of endotoxin on GH axis is mainly a pituitary one. The selective blockade of somatostatin should be useful for a better knowledge of the role of SRIH stimulation in the physiopathology of septic shock.
内毒素已被证明可刺激人类和绵羊的生长激素（GH）分泌。然而，内毒素对参与GH调节的下丘脑神经激素的影响从未在体内进行过研究。在绵羊中，可以收集垂体门脉血（HPB）并在生理条件下量化生长激素释放激素（GHRH）和生长抑素（SRIH）的分泌。本研究的目的是确定急性静脉注射内毒素对绵羊中这些肽分泌的影响。内毒素使完整公羊的GH持续增加（增加6.2±1.3倍）。与下丘脑 - 垂体 - 肾上腺轴相比，这种刺激出现延迟且不太明显。令人惊讶的是，GH的增加与颈静脉（增加10.6±2.4倍）和门脉（增加7.9±3倍）SRIH水平的显著升高相关，而GHRH没有显著增加。为了确定门脉SRIH的增加是否是GH短反馈增加的结果，我们在先前注射GHRH以耗尽垂体GH储备后研究了内毒素对GH的反应。在这种情况下，尽管内毒素治疗后GH没有增加，但SRIH水平显著升高。我们首次在绵羊中观察到颈静脉和门脉SRIH同时且幅度相近增加的实验情况。颈静脉SRIH的来源可能是胃肠道，全身循环中颈静脉SRIH释放增加可能部分导致垂体门脉SRIH增加。最终，我们的结果表明内毒素在多个水平上诱导了复杂反应，导致门脉和外周SRIH水平特异性增加。GHRH释放缺乏变化以及SRIH分泌增加与GH增加之间令人惊讶的关联表明，内毒素对GH轴的影响主要是垂体水平的。生长抑素的选择性阻断对于更好地了解SRIH刺激在脓毒性休克病理生理学中的作用应该是有用的。
