Bonavera J J, Kalra S P, Kalra P S
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville 32610-0294.
Endocrinology. 1993 Jul;133(1):178-82. doi: 10.1210/endo.133.1.8319564.
A large body of recent evidence suggests that a number of inhibitory and excitatory neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytokine [interleukin-1 beta (IL-1 beta)], or tachykinin [neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeks postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg) at 30-min intervals. Blood samples for LH measurements were withdrawn immediately before and 10 min after each NMDA injection. The results show that intracerebroventricular beta END, IL-1 beta, or NPK inhibited LH release. Multiple injections of NMDA did not alter the existing pattern of LH secretion in castrated control rats. However, similar NMDA injections completely prevented the decrease in LH release by beta END, IL-1 beta, or NPK. Plasma LH levels in these rats remained within the range seen in untreated control rats throughout the 120-min duration of the experiment, and NMDA injections at 30-min intervals evoked pulses of LH that resembled those seen normally in castrated rats. The blockade of the inhibitory effects of the three peptides by NMDA and previous knowledge of hypothalamic sites of NMDA action suggest that EAA systems may represent a common pathway down-stream in the hypothalamic LHRH-regulating circuitry to mediate diminution of LH release by inhibitory peptides. Further, their inhibitory influence may be exerted either directly at the level of LHRH neurons and/or by diminution in EAA efflux, leading to suppression of LHRH and LH release.
近期大量证据表明，一些抑制性和兴奋性神经肽及氨基酸可能参与去势大鼠下丘脑促黄体激素释放激素（LHRH）的间歇性分泌及垂体促黄体激素（LH）的分泌。然而，这些信使分子在控制LH分泌过程中的确切功能关系仍有待确定。本研究的目的是检验以下假设：阿片类物质[β-内啡肽（β END）]、细胞因子[白细胞介素-1β（IL-1β）]或速激肽[神经肽-K（NPK）]对LH释放的抑制作用是兴奋性氨基酸（EAA）信号减弱的结果。成年雄性大鼠被去势，并在第三脑室植入脑室内插管，以便在去势2周后给予β END（10微克/只大鼠）、NPK（2.5纳摩尔/只大鼠）或IL-1β（100纳克/只大鼠）。在实验前一天，大鼠接受心房插管，用于频繁采血以及每隔30分钟静脉注射谷氨酸受体激动剂N-甲基-D-天冬氨酸（NMDA；5毫克/千克）。在每次NMDA注射前及注射后10分钟立即采集用于测量LH的血样。结果显示，脑室内注射β END、IL-1β或NPK可抑制LH释放。多次注射NMDA并未改变去势对照大鼠现有的LH分泌模式。然而，类似的NMDA注射完全阻止了β END、IL-1β或NPK引起的LH释放减少。在整个120分钟的实验过程中，这些大鼠的血浆LH水平保持在未处理对照大鼠所见的范围内，每隔30分钟注射NMDA诱发的LH脉冲类似于去势大鼠正常所见的脉冲。NMDA对这三种肽抑制作用的阻断以及先前对NMDA作用的下丘脑部位的了解表明，EAA系统可能代表下丘脑LHRH调节回路下游的一条共同途径，以介导抑制性肽对LH释放的减少。此外，它们的抑制作用可能直接作用于LHRH神经元水平和/或通过减少EAA外流来发挥，从而导致LHRH和LH释放受到抑制。
