Tumor necrosis factor-alpha mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat.
Tumor necrosis factor-alpha mediates endotoxin induced suppression of gonadotropin-releasing hormone pulse generator activity in the rat.
复制标题
肿瘤坏死因子-α介导内毒素诱导的大鼠促性腺激素释放激素脉冲发生器活性的抑制。
作者：
Mi;M. Nishihara;Michio Takahashi
已知细菌内毒素脂多糖（LPS）可抑制促性腺激素分泌，这种作用被认为是由细胞因子介导的。在本研究中，我们研究是否LPS影响下丘脑电活动与LH脉冲，以及是否肿瘤坏死因子-α（TNF-α），LPS诱导的主要细胞因子，参与了这一过程。卵巢切除大鼠装有长期植入电极阵列在下丘脑内侧基底，和多单位活动（MUA）记录下清醒，无约束的条件下。每6分钟通过留置心房导管抽取血样或测定血清LH浓度。静脉注射（i. v.）注射LPS（1微克）在整个实验期间抑制与LH脉冲相关的MUA的特征性增加（齐射），直至5小时。LPS对MUA齐射的这种抑制作用通过侧脑室中的留置套管同时脑室内（icv）注射TNF-α抗体（50 ng）而显著减弱。MUA的这些变化忠实地反映在LH分泌模式中。此外，静脉注射（0.4-2微克）或静脉注射（20-250 ng）TNF-α抑制MUA齐射和相关的LH脉冲的频率以剂量依赖性的方式。这些结果表明，LPS通过涉及TNF-α的机制导致促性腺激素释放激素脉冲发生器活性的抑制。
Bacterial endotoxin lipopolysaccharide (LPS) is known to suppress gonadotropin secretion and this effect is assumed to be mediated by cytokines. In the present study, we examined whether LPS affected hypothalamic electrical activity associated with LH pulses, and whether tumor necrosis factor-alpha (TNF-alpha), a major cytokine induced by LPS, was involved in this process. Ovariectomized rats were fitted with chronically implanted electrode arrays in the mediobasal hypothalamus, and multiunit activity (MUA) was recorded under conscious, unrestrained conditions. Blood samples were withdrawn every 6 min through an indwelling atrial catheter or determining serum LH concentrations. Intravenous (i.v.) injection of LPS (1 microgram) suppressed characteristic increases (volleys) in MUA associated with LH pulses throughout the experimental period up to 5 h. This suppressive effect of LPS on MUA volleys was significantly attenuated by simultaneous intracerebroventricular (icv) injection of the antibody (50 ng) to TNF-alpha through an indwelling cannula in the lateral ventricle. These changes in MUA were faithfully reflected in the LH secretory pattern. Further, either i.v. (0.4-2 micrograms) or i.c.v. (20-250 ng) injection of TNF-alpha suppressed the frequency of MUA volleys and associated LH pulses in a dose-dependent manner. These results suggest that LPS leads to the suppression of gonadotropin-releasing hormone pulse generator activity through a mechanism involving TNF-alpha.
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影响因子：
158.5
作者：
MICHIE, HR;MANOGUE, KR;WILMORE, DW
通讯作者：
WILMORE, DW
大鼠脑室内注射重组人白细胞介素-1 诱导促肾上腺皮质激素释放：前列腺素可能参与。
影响因子：
4.8
作者：
Katsuura,G;Gottschall,PE;Dahl,RR;Arimura,A
通讯作者：
Arimura,A
前列腺素介导大鼠体内促肾上腺皮质激素对肿瘤坏死因子的反应。
影响因子：
4.8
作者：
Sharp,BM;Matta,SG
通讯作者：
Matta,SG
影响因子：
4.4
作者：
B. Beutler;I. Milsark;A. Cerami
通讯作者：
B. Beutler;I. Milsark;A. Cerami
影响因子：
4.4
作者：
I. Chung;E. Benveniste
通讯作者：
I. Chung;E. Benveniste