DePaolo L V, King R A, Carrillo A J
Endocrinology. 1987 Jan;120(1):272-9. doi: 10.1210/endo-120-1-272.
Recent evidence has been presented that demonstrates the existence of ultrashort feedback circuits for a number of neuropeptides in the central nervous system. The present investigation was undertaken to examine the possible existence of an autoregulatory mechanism for LHRH. In the first experiment, long term ovariectomized rats bearing lateral ventricular and atrial cannulae received intracerebroventricular (icv) injections of saline or LHRH every hour from 1200-1500 h. Blood was collected at 10-min intervals from 1200-1500 h to assess the effects of icv LHRH on pulsatile LH and FSH release. After the 1500 h collection, LHRH was injected iv and blood was collected to determine the effects of icv LHRH on pituitary responsiveness to LHRH. Central injections of 0.1 pg and 1 ng LHRH, but not 10 pg LHRH, significantly suppressed mean LH levels, trough LH levels, and LH pulse frequency compared to those in saline-treated control rats. The amplitude of LH pulses was not significantly affected by any dose of LHRH. In contrast to LH, multiple icv injections of LHRH failed to alter pulsatile FSH release. Pituitary LH and FSH responses to iv LHRH injection were not suppressed by icv LHRH. In a second experiment, hourly icv injections of 1 ng LHRH into proestrous rats markedly suppressed preovulatory LH release only during the middle to latter phases of the surge. In a final study using an in vitro superfusion system, addition of a LHRH agonist to the superfusion medium at a concentration that does not cross-react in the LHRH RIA suppressed basal and K+-stimulated LHRH release from medial basal hypothalamic fragments, but not from median eminence explants. These results support the existence and operation of an autoregulatory mechanism for LHRH in the central nervous system which may participate in the control of episodic LHRH release in ovariectomized rats and preovulatory LHRH release in proestrous rats. Seemingly, ultrashort-loop negative feedback regulation of LHRH requires the presence of structures other than nerve terminals in the MBH (i.e. cell bodies).
最近有证据表明，中枢神经系统中多种神经肽存在超短反馈回路。本研究旨在探讨促性腺激素释放激素（LHRH）是否存在自调节机制。在第一个实验中，长期卵巢切除且带有侧脑室和心房插管的大鼠，于12:00至15:00每小时接受一次脑室内（icv）注射生理盐水或LHRH。在12:00至15:00期间，每隔10分钟采集一次血液，以评估icv注射LHRH对促黄体生成素（LH）和促卵泡生成素（FSH）脉冲式释放的影响。在15:00采集后，静脉注射LHRH并采集血液，以确定icv注射LHRH对垂体对LHRH反应性的影响。与生理盐水处理的对照大鼠相比，脑室内注射0.1 pg和1 ng LHRH可显著抑制平均LH水平、LH谷值水平和LH脉冲频率，但10 pg LHRH则无此作用。任何剂量的LHRH对LH脉冲幅度均无显著影响。与LH不同，多次脑室内注射LHRH未能改变FSH的脉冲式释放。脑室内注射LHRH并未抑制垂体对静脉注射LHRH的LH和FSH反应。在第二个实验中，对动情前期大鼠每小时脑室内注射1 ng LHRH，仅在LH峰的中晚期显著抑制排卵前LH释放。在最后一项使用体外灌流系统的研究中，向灌流培养基中添加一种在LHRH放射免疫分析中无交叉反应的浓度的LHRH激动剂，可抑制内侧基底下丘脑碎片的基础和钾离子刺激的LHRH释放，但对正中隆起外植体无此作用。这些结果支持中枢神经系统中LHRH自调节机制的存在和作用，该机制可能参与去卵巢大鼠中LHRH的脉冲式释放以及动情前期大鼠排卵前LHRH释放的控制。显然，LHRH的超短环负反馈调节需要内侧基底下丘脑（MBH）中除神经末梢以外的结构（即细胞体）的存在。
