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下丘脑孤啡肽/痛敏肽在雌激素和孕激素预处理的去卵巢大鼠排卵前促黄体生成素激增中的作用。

Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats.

作者信息

An Xiao-fei, Yu Jiang-yi, Feng Yi, Chen Bo-ying, Zhang Su-lin

机构信息

Department of Endocrinology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China.

出版信息

Acta Pharmacol Sin. 2007 Aug;28(8):1189-97. doi: 10.1111/j.1745-7254.2007.00587.x.

Abstract

AIM

To investigate the role of hypothalamus nociceptin/orphanin FQ (OFQ) and its endogenous receptor, the opioid receptor-like1 receptor (ORL1 receptor) in the estrus cycle of female rats.

METHOD

Radioimmunoassay was used to detect the effect of the intracerebroventricular (icv) administration of OFQ and/or the ORL1 receptor antagonist [Nphe1]Nociceptin(1-13)NH2, that is, NC13 on luteinizing hormone (LH) levels of estrogen- and progesterone (EBP)-primed, ovariectomized (OVX) rats (EBP-primed OVX rats). RT-PCR, Western blotting, and immunohistochemistry techniques were adopted to observe the changes of OFQ and the ORL1 receptor in the pre-optic area (POA) and the medial basal hypothalamus (MBH) of the estrus cycle of female rat.

RESULTS

Pre-ovulatory LH surges in EBP-primed, OVX rats were significantly reduced by icv administration of 20 and 200 nmol OFQ (P<0.05), and the effect of 20 nmol OFQ could be abolished by pretreatment with 20 nmol NC13. The OFQ mRNA level in the POA on pro-estrus was lowered markedly compared to diestrus and estrus (P<0.05), while the mRNA and protein levels of the ORL1 receptor showed no significant changes in the POA and MBH across the estrus cycle. Meanwhile, the number of OFQ-immunoreactive neurons in the medial POA, ventromedial hypothalamus, and the arcuate nucleus on pro-estrus was significantly decreased compared to diestrus and estrus (P<0.05).

CONCLUSION

The inhibitory effect of OFQ on the LH surge of EBP-primed, OVX rats and its downregulation in POA and MBH on pro-estrus suggests that it might play a negative modulatory role in the estrus cycle.

摘要

目的

研究下丘脑孤啡肽/孤啡肽FQ(OFQ)及其内源性受体阿片样受体1(ORL1受体)在雌性大鼠发情周期中的作用。

方法

采用放射免疫分析法检测脑室内注射OFQ和/或ORL1受体拮抗剂[苯丙氨酸1]孤啡肽(1-13)NH2(即NC13)对雌激素和孕酮(EBP)预处理的去卵巢(OVX)大鼠(EBP预处理的OVX大鼠)黄体生成素(LH)水平的影响。采用逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法和免疫组织化学技术观察雌性大鼠发情周期中视前区(POA)和下丘脑内侧基底部(MBH)中OFQ和ORL1受体的变化。

结果

脑室内注射20和200 nmol OFQ可显著降低EBP预处理的OVX大鼠排卵前LH峰(P<0.05),20 nmol NC13预处理可消除20 nmol OFQ的作用。与动情间期和发情期相比,发情前期POA中OFQ mRNA水平显著降低(P<0.05),而整个发情周期中POA和MBH中ORL1受体的mRNA和蛋白质水平无显著变化。同时,与动情间期和发情期相比,发情前期内侧POA、腹内侧下丘脑和弓状核中OFQ免疫反应性神经元数量显著减少(P<0.05)。

结论

OFQ对EBP预处理的OVX大鼠LH峰的抑制作用及其在发情前期POA和MBH中的下调表明,它可能在发情周期中起负性调节作用。

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