Systemic challenge with endotoxin stimulates corticotropin-releasing hormone and arginine vasopressin secretion into hypophyseal portal blood:: Coincidence with gonadotropin-releasing hormone suppression
Systemic challenge with endotoxin stimulates corticotropin-releasing hormone and arginine vasopressin secretion into hypophyseal portal blood:: Coincidence with gonadotropin-releasing hormone suppression
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DOI：
10.1210/en.139.10.4175
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发表时间：
1998-10-01
期刊：
影响因子：
4.8
通讯作者：
Karsch, FJ
中科院分区：
文献类型：
--
作者：
Battaglia, DF;Brown, ME;Karsch, FJ
我们测试的假设，全身免疫/炎症的挑战（内毒素）激活神经内分泌应激轴中枢刺激分泌CRH和精氨酸加压素（AVP）到垂体门静脉血。此外，我们还研究了应激神经肽的刺激与脉冲性GnRH和LH分泌抑制之间的时间关联。使用警觉，行为正常的母羊，垂体门静脉和外周血采样，同时在10分钟的时间间隔为14小时。以相同的时间间隔通过遥测技术远程监测温度。在4小时基线期后注射内毒素（400 ng/kg，静脉推注）或生理盐水作为对照。门静脉血测定CRH，AVP和GnRH，外周血测定皮质醇，孕酮和LH。在对照组中，垂体门静脉CRH和AVP保持略高于或处于测定灵敏度，皮质醇显示出不受生理盐水影响的规则节律模式，是典型的基础分泌。相反，内毒素强烈刺激CRH和AVP分泌到门静脉血，皮质醇和孕酮分泌到外周血。CRH和AVP通常同时上升和下降，尽管AVP反应的峰值约为CRH的10倍。门静脉血中的AVP不是由于垂体后叶腺分泌到外周循环中的激素再循环造成的，因为相对于门静脉血的显着增加，外周血中的AVP增加可以忽略不计。CRH和AVP的刺激正好与显着抑制GnRH和LH脉冲式分泌在这些相同的母羊和发热的产生。我们的结论是，内毒素诱导中枢激活的神经内分泌应激轴，刺激CRH和AVP释放到垂体门静脉血的意识，正常行为的母羊。这种反应在时间上与抑制GnRH和LH的脉动释放以及刺激肾上腺皮质醇和孕酮分泌和发热有关。
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, iv 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.