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对氯苯丙氨酸对雌激素处理的去卵巢大鼠下丘脑吲哚胺水平以及儿茶酚胺动力学和促黄体生成素激增中发生的相关变化的影响。

Effects of p-chlorophenylalanine on hypothalamic indoleamine levels and the associated changes which occur in catecholamine dynamics and LH surges in estrogen-treated ovariectomized rats.

作者信息

Burri R, Petersen S L, Barraclough C A

出版信息

Brain Res. 1987 Jul 28;416(2):267-76. doi: 10.1016/0006-8993(87)90906-1.

DOI:10.1016/0006-8993(87)90906-1
PMID:2441813
Abstract

Recent studies have demonstrated that the serotonergic and noradrenergic systems are functionally and anatomically linked and both systems have been implicated as contributors to the regulation of the phasic release of LH. Consequently, perturbations within the serotonergic system could secondarily affect noradrenergic system activity and result in a loss of phasic LHRH secretion. In the present studies we examined the effects of p-chlorophenylalanine (PCPA) on LH surges and the associated changes which occur in hypothalamic serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations. We also evaluated the effects of this drug on norepinephrine (NE) and dopamine (DA) initial concentrations, rate constants and turnover rates in the medial preoptic area (MPN), suprachiasmatic nuclei (SCN), paraventricular nuclei (PVN) and median eminence (ME). Seven days after ovariectomy, rats received estradiol (E2) capsules (day 0) and on day 1 some animals also received PCPA (250 mg/kg b. wt., i.p.) while the remainder served as controls. LH surges occurred in control animals but not in PCPA-treated rats on days 2, 3 and 4. PCPA produced a significant decline in 5-HT and 5-HIAA concentrations in all microdissected hypothalamic regions at 09.00 and 15.00 h on day 2. In control rats, there were no significant changes in initial concentrations of NE in the MPN, PVN and ME between 09.00 and 15.00 h with the exception of the SCN where a slight decline had occurred by 15.00 h. NE rate constants and turnover rates increased during the afternoon in controls in the MPN, SCN and ME and declined in the PVN concomitant with LH surges. PCPA had variable effects in suppressing NE initial concentrations depending upon the hypothalamic area studied and the time of day. More importantly, the drug abolished the diurnal rhythm in rate constants observed in controls and consequently, neither the MPN, SCN nor ME showed any increase in NE turnover rates in the afternoon of day 2. In contrast, a significant decline in rate constants and turnover rates occurred in the PVN of both control and PCPA-treated rats during the afternoon of day 2. DA initial concentrations declined in controls between 09.00 and 15.00 h in the MPN and ME but not in the SCN or PVN.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

近期研究表明,血清素能系统和去甲肾上腺素能系统在功能和解剖结构上相互关联,且这两个系统均被认为参与了促黄体生成素(LH)的阶段性释放调节。因此,血清素能系统内的紊乱可能继而影响去甲肾上腺素能系统的活性,并导致促性腺激素释放激素(LHRH)阶段性分泌的丧失。在本研究中,我们检测了对氯苯丙氨酸(PCPA)对LH峰以及下丘脑血清素(5-HT)和5-羟吲哚乙酸(5-HIAA)浓度相关变化的影响。我们还评估了该药物对内侧视前区(MPN)、视交叉上核(SCN)、室旁核(PVN)和正中隆起(ME)中去甲肾上腺素(NE)和多巴胺(DA)初始浓度、速率常数及周转率的影响。卵巢切除术后7天,大鼠接受雌二醇(E2)胶囊植入(第0天),在第1天,部分动物还接受PCPA(250mg/kg体重,腹腔注射),其余作为对照。对照组动物在第2、3和4天出现LH峰,而PCPA处理的大鼠未出现。在第2天的09:00和15:00,PCPA使所有显微解剖的下丘脑区域中的5-HT和5-HIAA浓度显著下降。在对照大鼠中,09:00至15:00期间,MPN、PVN和ME中的NE初始浓度无显著变化,但SCN除外,在15:00时略有下降。在对照组中,下午期间MPN、SCN和ME中的NE速率常数和周转率增加,PVN中的则下降,同时伴有LH峰。根据所研究的下丘脑区域和一天中的时间,PCPA在抑制NE初始浓度方面有不同的效果。更重要的是,该药物消除了对照组中观察到的速率常数的昼夜节律,因此,在第2天下午,MPN、SCN和ME中的NE周转率均未增加。相反,在第2天下午,对照和PCPA处理大鼠的PVN中速率常数和周转率均显著下降。在对照组中,09:00至15:00期间,MPN和ME中的DA初始浓度下降,但SCN或PVN中未下降。(摘要截短至400字)

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