Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis
Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis
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DOI：
10.1530/rep-19-0025
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发表时间：
2019-07-01
期刊：
影响因子：
3.8
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Xuan Phuoc Nguyen;Nakamura, Tomoko;Kikkawa, Fumitaka
卵泡发生是一个复杂的过程，由原始种群的卵泡生长和发育定义。颗粒细胞（GC）通过增殖、获得促性腺激素反应性、类固醇生成和产生自分泌/旁分泌因子在卵泡生长的每个阶段中起重要作用。最近发现的下丘脑神经肽phoenixin参与生殖系统的调节。Phoenixin通过其受体G蛋白偶联受体173（GPR 173）激活cAMP/PKA通路，导致CREB（pCREB）磷酸化。在这里，我们展示了凤凰素和GPR 173在人卵巢中的表达模式，并探讨其在卵泡发生中的作用。Phoenixin和GPR 173均在人卵泡中表达，并且随着卵泡的生长在GC中表达增加。100 nM的Phoenixin处理24 h可诱导人非黄素化颗粒细胞系HGrC 1增殖，并显著增加CYP 19 A1、FSHR、LHR和KITL的表达水平，但降低NPPC的表达水平。这些作用被GPR 173 siRNA抑制。结果表明，凤凰霉素处理后，CREB 1、pCREB的表达水平和雌二醇（E2）的分泌均呈浓度依赖性增加。在小鼠卵巢组织培养模型中，Phoenixin还显著增加了卵泡面积，导致具有更高成熟水平的排卵卵母细胞数量增加。总之，我们的数据表明，凤凰毒素是一种卵巢内因子，通过其受体GPR 173促进卵泡生长，加速GC增殖，诱导E2产生和增加卵泡发育相关基因的表达。
Folliculogenesis is a complex process, defined by the growth and development of follicles from the primordial population. Granulosa cells (GCs) play a vital role in every stage of follicular growth through proliferation, acquisition of gonadotropic responsiveness, steroidogenesis and production of autocrine/paracrine factors. A recently discovered hypothalamic neuropeptide phoenixin is involved in the regulation of the reproductive system. Phoenixin acts through its receptor, G protein-coupled receptor 173 (GPR173), to activate the cAMP/PKA pathway leading to the phosphorylation of CREB (pCREB). Here, we demonstrated the expression patterns of phoenixin and GPR173 in human ovary and explored its role in folliculogenesis. Phoenixin and GPR173 were both expressed in the human ovarian follicle, with increased expression in GCs as the follicle grows. Phoenixin treatment at 100 nM for 24 h induced the proliferation of human non-luteinized granulosa cell line, HGrC1 and significantly increased the expression levels of CYP19A1, FSHR, LHR and KITL, but decreased NPPC expression levels. These effects were suppressed by GPR173 siRNA. The expression level of CREB1, pCREB and estradiol (E2) production in the culture medium was significantly enhanced by phoenixin treatment in a concentration-dependent manner. Phoenixin also significantly increased the follicular area in a murine ovarian tissue culture model, leading to an increased number of ovulated oocytes with a higher level of maturation. Taken together, our data demonstrate that phoenixin is an intraovarian factor that promotes follicular growth through its receptor GPR173 by accelerating proliferation of GCs, inducing E2 production and increasing the expression of genes related to follicle development.