LH调节女性雄激素生成的分子信号通路研究进展

发布时间：2018-07-13 20:19

【摘要】：卵巢雄激素合成于卵泡膜细胞,并依赖于黄体生成激素(LH)的刺激作用,由LH下游众多信号通路精密调控,包括传统的环磷酸腺苷-蛋白激酶A-环磷酸腺苷反应元件结合蛋白(c AMP-PKA-CREB)、PKA-细胞外调节蛋白激酶(ERK)、Ras-Raf-MEK-ERK、磷脂酰肌醇3激酶(PI3K)-Akt等信号通路。卵泡发育过程中,磷脂酶Cβ-磷酸肌醇(PLCβ-IP)通路经非腺苷酸环化酶依赖途径激活,介导LH峰作用下颗粒细胞的最终分化。近年研究发现,Wnt、m TORC1等经典信号通路也与卵巢雄激素调节有关,并与其他经典信号通路之间存在复杂的网状交互作用,共同调控卵泡膜细胞雄激素生成。转录调节因子SET作为多任务蛋白,在多种组织中广泛表达,在卵泡膜细胞中通过抑制下游PP2A增加雄激素生成酶P450c17裂解酶活性,促进雄激素合成。LH调控通路过度激活与多种内分泌疾病(如多囊卵巢综合征)有关,并参与妊娠期糖尿病、胰岛素抵抗等多种病理过程。阐明卵泡膜细胞雄激素调控通路对解释雄激素相关疾病尤为重要,是寻找相应疾病治疗方法的基础。就LH作用于卵巢卵泡膜细胞调节雄激素生成的主要通路进行综述。
[Abstract]:The ovarian androgen is synthesized in the follicular membrane cells and depends on the stimulating effect of luteinizing hormone (LH), which is precisely regulated by many signal pathways downstream of LH. These signaling pathways include the traditional cyclic adenosine monophosphate protein kinase A- cyclic adenosine responsive element binding protein (c AMP-PKA-CREB) PKA- extracellular regulated protein kinase (ERK) Ras-Raf-MEK-ERK, phosphatidylinositol 3 kinase (PI3K) -Akt and so on. During follicular development, phospholipase C 尾 -phosphate inositol (PLC 尾 -IP) pathway is activated by non-adenylate cyclase dependent pathway, which mediates the final differentiation of granulosa cells under the action of LH peak. In recent years, it has been found that some classical signal pathways, such as Wntttim TORC1, are also related to the regulation of ovarian androgen, and there are complex reticular interactions between them and other classical signal pathways to regulate androgen production in theca follicular cells. As a multitasking protein, set, a transcriptional regulator, is widely expressed in many tissues and increases the activity of androgen-producing enzyme P450c17 by inhibiting downstream PP2A in follicular membrane cells. The over-activation of androgen synthesis. LH regulatory pathway is associated with many endocrine diseases (such as polycystic ovary syndrome) and is involved in many pathological processes such as gestational diabetes mellitus insulin resistance and so on. It is very important to elucidate the androgen regulation pathway of follicular membrane cells in order to explain androgen related diseases. This paper reviews the main pathways of LH acting on ovarian follicular membrane cells to regulate androgen production.
【作者单位】：南京医科大学第一附属医院生殖医学科;
【基金】：国家自然科学基金(81200414) 江苏省卫生厅项目(ZX201110,FXK201221)
【分类号】：R339.22

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