The chronic intracerebroventricular infusion of interleukin-1 beta alters the activity of the hypothalamic-pituitary-gonadal axis of cycling rats. I. Effect on LHRH and gonadotropin biosynthesis and secretion.
The chronic intracerebroventricular infusion of interleukin-1 beta alters the activity of the hypothalamic-pituitary-gonadal axis of cycling rats. I. Effect on LHRH and gonadotropin biosynthesis and secretion.
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DOI：
10.1210/endo.133.6.8243260
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发表时间：
1993-12
期刊：
影响因子：
4.8
通讯作者：
Serge Rivest;S. Lee;B. Attardi;C. Rivier
中科院分区：
文献类型：
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作者：
Serge Rivest;S. Lee;B. Attardi;C. Rivier
我们以前曾报道，急性注射白细胞介素-1 β（IL-1 β）到完整的雌性大鼠的脑室迅速减少LHRH的释放和抑制这种肽在内侧视前区（MPOA）的基因表达。因此，本研究旨在确定连续暴露于细胞因子是否会破坏发情周期。以4 ng/h的速率脑室内注射IL-1 β 4-6天。每日阴道涂片，以跟踪周期;定期测量垂体LH和FSH分泌。在治疗结束时测量垂体中LH和FSH信使RNA（mRNA）的稳态水平以及MPOA中LHRH基因表达。输注IL-1 β导致发情周期完全中断，其特征在于持续的涂片指示间情期。当与用溶剂处理的动物相比时，输注IL-1 β的大鼠显示循环LH浓度显著降低，这伴随着垂体中mRNA水平降低。这种统计学差异（P < 0.01）持续存在，即使在周期的类似阶段（即间情期）将给药大鼠与对照组进行比较。IL-1 β输注后，血浆FSH水平始终保持较低水平，但在对照动物中显示出预期的周期性变化。在治疗结束时，LHRH基因的表达也显着抑制LHRH神经元之间的嘴侧视前区/终板的血管器和这些动物的MPOA分布。这些结果表明，IL-1 β长时间输注到脑室破坏了发情周期，这是一个伴随LHRH和促性腺激素生物合成/释放减少的事件。我们在一项相关的研究中报道，IL-1治疗的大鼠也显示出血浆孕酮水平升高。然而，这是不可能的，这种变化是负责中断的周期在这里描述的，事实上，我们以前已经观察到，中央管理的IL-1 β完整的大鼠导致立即封锁的自发活动的LHRH胞体在下午的发情前期和显着降低LHRH mRNA水平在性腺切除动物。综上所述，这些数据表明，IL-1 β的主要作用是在LHRH胞体的水平，并且所导致的周期中断是由LHRH神经元活性改变和促性腺激素分泌减弱引起的。
We have previously reported that the acute injection of interleukin-1 beta (IL-1 beta) into the brain ventricles of intact female rats promptly decreases LHRH release and inhibits gene expression of this peptide in the medial preoptic area (MPOA). The present studies were therefore designed to determine whether continuous exposure to the cytokine would disrupt the estrous cycle. IL-1 beta was injected intracerebroventricularly for 4-6 days at a rate of 4 ng/h. Daily vaginal smears were obtained to follow the cycle; pituitary LH and FSH secretion were measured at regular intervals. Steady state levels of LH and FSH messenger RNA (mRNA) in the pituitary, and LHRH gene expression in the MPOA, were measured at the end of the treatment. Infusion of IL-1 beta caused a total disruption of the estrous cycle, characterized by persistent smears indicative of the diestrus stage. When compared to animals treated with the vehicle, rats infused with IL-1 beta showed a significant decrease in circulating LH concentrations, which was accompanied by lowered mRNA levels in the pituitary. This statistical difference (P < 0.01) persisted even when treated rats were compared to control in a similar stage of the cycle (i.e. diestrus). Plasma FSH levels remained low at all times after IL-1 beta infusion but showed the expected cyclic changes in control animals. At the end of treatment, LHRH gene expression was also markedly suppressed in LHRH neurons distributed between the rostral preoptic area/organum vasculosum of the lamina terminalis and the MPOA of these animals. These results indicate that prolonged infusion of IL-1 beta into brain ventricles disrupts the estrous cycle, an event accompanied by decreased biosynthesis/release of LHRH and gonadotropins. We report in a related study that IL-1-treated rats also show increased plasma progesterone levels. However, it is improbable that this change was responsible for the interruption of the cycle described here; indeed we have previously observed that the central administration of IL-1 beta to intact rats resulted in an immediate blockade of the spontaneous activity of LHRH perikarya during the afternoon of proestrus and significantly decreased LHRH mRNA levels in gonadectomized animals. Taken together, these data suggest that the primary effect of IL-1 beta is at the level of LHRH perikarya, and that the resulting interruption of the cycle is caused by altered LHRH neuronal activity and blunted gonadotropin secretion.