Battaglia D F, Brown M E, Krasa H B, Thrun L A, Viguié C, Karsch F J
Department of Physiology, University of Michigan, Ann Arbor 48109-0404, USA.
Endocrinology. 1998 Oct;139(10):4175-81. doi: 10.1210/endo.139.10.6226.
We tested the hypothesis that systemic immune/inflammatory challenge (endotoxin) activates the neuroendocrine stress axis centrally by stimulating the secretion of CRH and arginine vasopressin (AVP) into hypophyseal portal blood. In addition, we examined the temporal association between this stimulation of the stress neuropeptides and the inhibition of pulsatile GnRH and LH secretion. Using alert, normally behaving ewes, hypophyseal portal and peripheral blood were sampled simultaneously at 10-min intervals for 14 h. Temperature was monitored remotely by telemetry at the same interval. Endotoxin (400 ng/kg, i.v. bolus) or saline as a control was injected after a 4-h baseline period. Portal blood was assayed for CRH, AVP, and GnRH, and peripheral blood was assayed for cortisol, progesterone, and LH. In controls, hypophyseal portal CRH and AVP remained just above or at assay sensitivity, and cortisol showed a regular rhythmic pattern unaffected by saline and typical of basal secretion. In contrast, endotoxin potently stimulated CRH and AVP secretion into portal blood, and cortisol and progesterone into peripheral blood. Both CRH and AVP generally rose and fell simultaneously, although the peak of the AVP response was approximately 10-fold greater than that of CRH. The AVP in portal blood was not due to recirculation of hormone secreted into the peripheral circulation by the posterior pituitary gland, because the AVP increase in peripheral blood was negligible relative to the marked increase in portal blood. The stimulation of CRH and AVP coincided with significant suppression of GnRH and LH pulsatile secretion in these same ewes and with the generation of fever. We conclude that endotoxin induces central activation of the neuroendocrine stress axis, stimulating both CRH and AVP release into the hypophyseal portal blood of conscious, normally behaving ewes. This response is temporally coupled to inhibition of pulsatile GnRH and LH release as well as with stimulation of adrenal cortisol and progesterone secretion and generation of fever.
全身性免疫/炎症刺激（内毒素）通过刺激促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）分泌进入垂体门脉血，从而在中枢激活神经内分泌应激轴。此外，我们研究了这种应激神经肽的刺激与促性腺激素释放激素（GnRH）和促黄体生成素（LH）脉冲式分泌抑制之间的时间关联。使用警觉且行为正常的母羊，在14小时内每隔10分钟同时采集垂体门脉血和外周血样本。同时通过遥测以相同间隔远程监测体温。在4小时的基线期后，静脉推注注射内毒素（400 ng/kg）或生理盐水作为对照。检测垂体门脉血中的CRH、AVP和GnRH，以及外周血中的皮质醇、孕酮和LH。在对照组中，垂体门脉血中的CRH和AVP仅略高于或处于检测灵敏度水平，皮质醇呈现出不受生理盐水影响的规律节律模式，这是基础分泌的典型特征。相比之下，内毒素强烈刺激CRH和AVP分泌进入门脉血，以及皮质醇和孕酮分泌进入外周血。CRH和AVP通常同时升高和下降，尽管AVP反应的峰值比CRH的峰值大约高10倍。门脉血中的AVP并非由于后叶垂体分泌到外周循环中的激素再循环所致，因为外周血中AVP的增加相对于门脉血中的显著增加可忽略不计。CRH和AVP的刺激与这些相同母羊中GnRH和LH脉冲式分泌的显著抑制以及发热的产生同时发生。我们得出结论，内毒素诱导神经内分泌应激轴的中枢激活，并刺激CRH和AVP释放进入清醒且行为正常的母羊的垂体门脉血。这种反应在时间上与GnRH和LH脉冲式释放的抑制以及肾上腺皮质醇和孕酮分泌的刺激以及发热的产生相关联。
