Xu B, Pu S, Kalra P S, Hyde J F, Crowley W R, Kalra S P
Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610, USA.
Endocrinology. 1996 Dec;137(12):5297-302. doi: 10.1210/endo.137.12.8940349.
Both neuropeptide Y (NPY) and galanin (GAL) systems have been implicated in the excitatory regulation of pulsatile LH secretion in the ovariectomized rat. The present studies were designed to examine the possible interaction of these two neuropeptides in controlling episodic LH release by testing the effects of central infusion of antibodies (Ab) to NPY and GAL, alone or in combination; additional studies tested the effects of central administration of an antisense oligodeoxynucleotide (ODN) to NPY and GAL messenger RNA. Rats were ovariectomized, implanted with a cannula in the third ventricle, and used in experiments 2 weeks later. Central infusion, via Alzet osmotic minipumps, of IgG purified from an NPY Ab produced a dose-related suppression of pulsatile LH secretion. Although an Ab dilution of 1:10 was ineffective, a maximal inhibitory effect was obtained using an NPY Ab dilution of 1:1, which decreased the mean levels, pulse frequency, and pulse amplitude of LH. These parameters of episodic LH secretion were also significantly reduced by central injection of antisense NPY ODN compared to those in vehicle- or missense ODN-treated controls. Similar dose-related inhibitory effects on the parameters of LH secretion were seen after central infusion of GAL Ab. Furthermore, infusion of a combination of NPY Ab and GAL Ab, each at the ineffective dilution of 1:10, resulted in a profound inhibition of LH secretion equivalent to the pattern seen with the maximally effective 1:1 Ab dilution. These results strengthen the idea of a physiological role for both NPY and GAL systems in the mechanism underlying the LHRH pulse generator activity and further suggest that these two excitatory neuropeptides act in concert to generate pulsatile LHRH release.
神经肽Y（NPY）和甘丙肽（GAL）系统均与去卵巢大鼠促黄体生成素（LH）脉冲式分泌的兴奋性调节有关。本研究旨在通过测试向中枢注射NPY和GAL抗体（Ab）单独或联合使用的效果，来检验这两种神经肽在控制LH脉冲式释放中的可能相互作用；另外的研究测试了向中枢注射针对NPY和GAL信使核糖核酸（mRNA）的反义寡脱氧核苷酸（ODN）的效果。将大鼠去卵巢，在第三脑室植入套管，2周后用于实验。通过Alzet渗透微型泵向中枢注射从NPY Ab纯化的IgG，可产生与剂量相关的LH脉冲式分泌抑制作用。虽然1:10的Ab稀释度无效，但使用1:1的NPY Ab稀释度可获得最大抑制效果，这降低了LH的平均水平、脉冲频率和脉冲幅度。与载体或错义ODN处理的对照组相比，向中枢注射反义NPY ODN也显著降低了LH脉冲式分泌的这些参数。向中枢注射GAL Ab后，对LH分泌参数也观察到类似的剂量相关抑制作用。此外，以无效的1:10稀释度分别注射NPY Ab和GAL Ab的组合，导致LH分泌受到深度抑制，其模式与最大有效1:1 Ab稀释度所见相同。这些结果强化了NPY和GAL系统在促性腺激素释放激素（LHRH）脉冲发生器活动机制中具有生理作用的观点，并进一步表明这两种兴奋性神经肽协同作用以产生LHRH脉冲式释放。
