Pau K Y, Hess D L, Kaynard A H, Ji W Z, Gliessman P M, Spies H G
Division of Reproductive Biology and Behavior, Oregon Regional Primate Research Center, Beaverton 97006.
Endocrinology. 1989 Feb;124(2):891-8. doi: 10.1210/endo-124-2-891.
In gonadectomized animals, pulses of LH are secreted concurrently with pulsatile hypothalamic GnRH and it is hypothesized that pulses of GnRH are either driven or modulated by episodes of catecholamine release. The objective of this study was to determine if the alpha-adrenergic antagonist phentolamine (PHEN) can simultaneously block the release of GnRH and LH in ovariectomized (OVX) rhesus macaques. In Exp 1, simultaneous peripheral blood and mediobasal hypothalamic push-pull perfusion (PPP) samples were collected remotely at 10-min intervals for 24 h via a swivel/tether device in eight conscious, freely moving OVX rhesus monkeys. Phentolamine was continuously infused iv for 6 h at the rate of 4 mg/kg BW.h in five animals and 20 mg/kg BW.h in three animals. Infusion started at 6 h after the commencement of PPP. Sampling of PPP and blood continued for 12 h after the cessation of PHEN infusion. Exp 2 was carried out to determine if PHEN affects pituitary responsiveness to exogenous GnRH under conditions similar to those in Exp 1. Exogenous GnRH (5 micrograms, iv) was injected as a single bolus at 10-h intervals before, during, and after either a saline (4 ml/h for 6 h) infusion or, 3 weeks later, a PHEN infusion (4 mg/kgBW.h for 6 h) in three OVX females. The results of Exp 1 show that pulsatile patterns of hypothalamic GnRH and LH were either dampened or abolished by PHEN infusion. During the recovery period after PHEN infusion, pulse amplitudes of LH were enhanced, but pulse amplitudes of endogenous GnRH did not differ, as compared to those of corresponding LH and GnRH before infusion of PHEN. Data from Exp 2 suggested that the alpha-adrenergic blocking agent had no effect on the pituitary LH response to exogenous GnRH administration. These results directly support the hypothesis that adrenergic neuronal activities are critical for the pulsatile release of hypothalamic GnRH which governs the pulsatile release of LH in gonadectomized animals.
在性腺切除的动物中，促黄体生成素（LH）脉冲与下丘脑促性腺激素释放激素（GnRH）脉冲同时分泌，据推测，GnRH脉冲受儿茶酚胺释放事件驱动或调节。本研究的目的是确定α-肾上腺素能拮抗剂酚妥拉明（PHEN）是否能同时阻断去卵巢（OVX）恒河猴体内GnRH和LH的释放。在实验1中，通过旋转/系绳装置，每隔10分钟对8只清醒、自由活动的去卵巢恒河猴进行一次远程外周血和下丘脑基底部推挽灌注（PPP）样本采集，持续24小时。5只动物以4mg/kg体重·小时的速率静脉持续输注酚妥拉明6小时，3只动物以20mg/kg体重·小时的速率输注。输注在PPP开始6小时后开始。酚妥拉明输注停止后，PPP和血液样本采集持续12小时。进行实验2以确定在与实验1相似的条件下，PHEN是否影响垂体对外源性GnRH的反应。在3只去卵巢雌性动物中，在生理盐水（4ml/小时，持续6小时）输注前、期间和之后，或3周后酚妥拉明输注（4mg/kg体重·小时，持续6小时）前、期间和之后，每隔10小时静脉注射一次单剂量外源性GnRH（5微克）。实验1的结果表明，酚妥拉明输注可减弱或消除下丘脑GnRH和LH的脉冲模式。在酚妥拉明输注后的恢复期，LH的脉冲幅度增强，但与酚妥拉明输注前相应的LH和GnRH相比，内源性GnRH的脉冲幅度没有差异。实验2的数据表明，α-肾上腺素能阻断剂对外源性GnRH给药后的垂体LH反应没有影响。这些结果直接支持了以下假设：在性腺切除的动物中，肾上腺素能神经元活动对于下丘脑GnRH的脉冲释放至关重要，而下丘脑GnRH的脉冲释放控制着LH的脉冲释放。
