Gore A C, Terasawa E
Neuroscience Training Program and Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI, USA.
J Neuroendocrinol. 2001 Mar;13(3):239-48. doi: 10.1046/j.1365-2826.2001.00618.x.
We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the alpha1 and alpha2 but not beta receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an alpha1- or alpha2-adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by alpha1 and alpha2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate-serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems.
我们使用去卵巢豚鼠研究了三种参与调节促黄体生成素（LH）脉冲式释放的神经递质：阿片肽、5-羟色胺和去甲肾上腺素。由于其LH脉冲具有规律性，该豚鼠模型很有吸引力，能够清晰地确定任何干扰情况。在所有实验中，单独或依次给予特异性激动剂或拮抗剂以检测相互作用，并通过PULSAR分析确定其对LH平均浓度、脉冲幅度和脉冲间期的影响。在去卵巢豚鼠中，儿茶酚胺具有刺激作用（与其他物种不同，其通过α1和α2受体而非β受体起作用），阿片类物质具有抑制作用，5-羟色胺对LH脉冲式释放具有允许性刺激作用。阿片拮抗剂的刺激作用不会被α1或α2肾上腺素能拮抗剂预处理所阻断。同样，阿片拮抗剂预处理也不能阻止α1和α2拮抗剂对LH释放的抑制作用。这表明，在豚鼠中，阿片类物质和儿茶酚胺对LH释放的作用是通过独立于促黄体生成素释放激素（LHRH）神经元的途径发挥的。对于阿片-5-羟色胺相互作用，5-羟色胺能拮抗剂预处理不会阻断阿片拮抗剂对LH释放的刺激作用。然而，5-羟色胺能激动剂无法克服阿片激动剂的预处理作用。这表明5-羟色胺系统对LHRH释放的作用可能由阿片神经元间接介导。综上所述，这些研究表明所研究的三种神经递质系统在雌性豚鼠正常的LH脉冲式释放中起关键作用，并揭示了阿片系统与肾上腺素能和5-羟色胺能系统之间新的功能关系。
