RFamide-Related Peptide-3 Receptor Gene Expression in GnRH and Kisspeptin Neurons and GnRH-Dependent Mechanism of Action
RFamide-Related Peptide-3 Receptor Gene Expression in GnRH and Kisspeptin Neurons and GnRH-Dependent Mechanism of Action
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DOI：
10.1210/en.2012-1133
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发表时间：
2012-08-01
期刊：
影响因子：
4.8
通讯作者：
Anderson, Greg M.
中科院分区：
文献类型：
--
作者：
Rizwan, Mohammed Z.;Poling, Matthew C.;Anderson, Greg M.
已知RFamide相关肽-3（RFRP-3）抑制GnRH神经元的活性。目前尚不清楚其G蛋白偶联受体GPR 147和GPR 74是否存在于GnRH神经元或GnRH神经元网络的传入输入上，或者RFRP-3是否可以独立于GnRH抑制促性腺激素分泌。我们测试了以下内容：1）GnRH是否是RFRP-3对LH分泌的影响所必需的; 2）RFRP-3神经元是否投射到小鼠的GnRH和吻侧室周神经元; 3）这些神经元是否表达Gpr 147和Gpr 74。静脉注射GPR 147拮抗剂RF 9可增加去势雄性大鼠的血浆LH浓度，但在GnRH拮抗剂西曲瑞克存在下无法做到这一点。双标记免疫组化显示，约26%的GnRH神经元从男性和动情间期的女性小鼠并置的RFRP-3纤维，和19%的kisspeptin神经元从动情前期的女性小鼠并置的RFRP-3纤维。使用GnRH和kisspeptin细胞的免疫磁性纯化，单细胞巢式RT-PCR和原位杂交，我们发现，33%的GnRH神经元和9-16%的吻侧脑室周围kisspeptin神经元表达Gpr 147，而Gpr 74在两个群体中均不表达。这些数据表明，RFRP-3可以在两个水平的GnRH神经元网络（即GnRH神经元和吻肽的头端室周神经元）调节生殖，但不能抑制促性腺激素分泌的GnRH独立。（内分泌学153：3770-3779，2012）
RFamide-related peptide-3 (RFRP-3) is known to inhibit the activity of GnRH neurons. It is not yet clear whether its G protein-coupled receptors, GPR147 and GPR74, are present on GnRH neurons or on afferent inputs of the GnRH neuronal network or whether RFRP-3 can inhibit gonadotropin secretion independently of GnRH. We tested the following: 1) whether GnRH is essential for the effects of RFRP-3 on LH secretion; 2) whether RFRP-3 neurons project to GnRH and rostral periventricular kisspeptin neurons in mice, and 3) whether Gpr147 and Gpr74 are expressed by these neurons. Intravenous treatment with the GPR147 antagonist RF9 increased plasma LH concentration in castrated male rats but was unable to do so in the presence of the GnRH antagonist cetrorelix. Dual-label immunohistochemistry revealed that approximately 26% of GnRH neurons from male and diestrous female mice were apposed by RFRP-3 fibers, and 19% of kisspeptin neurons from proestrous female mice were apposed by RFRP-3 fibers. Using immunomagnetic purification of GnRH and kisspeptin cells, single-cell nested RT-PCR, and in situ hybridization, we showed that 33% of GnRH neurons and 9-16% of rostral periventricular kisspeptin neurons expressed Gpr147, whereas Gpr74 was not expressed in either population. These data reveal that RFRP-3 can act at two levels of the GnRH neuronal network (i.e. the GnRH neurons and the rostral periventricular kisspeptin neurons) to modulate reproduction but is unable to inhibit gonadotropin secretion independently of GnRH. (Endocrinology 153: 3770-3779, 2012)