Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active
Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active
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DOI：
10.1016/j.rbmo.2016.03.003
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发表时间：
2016-06-01
影响因子：
4
通讯作者：
Bernal, Andres Lopez
中科院分区：
文献类型：
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作者：
Kanamarlapudi, Venkateswarlu;Gordon, Uma D.;Bernal, Andres Lopez
多囊卵巢综合征（PCOS）与无排卵性不孕症有关。促黄体生成素/绒毛膜促性腺激素受体（LHCGR），这是排卵的关键，已被认为是过早表达在PCOS妇女的卵泡。本研究旨在分析LHCGR在PCOS患者卵巢颗粒细胞中的表达和活性，以及ARF 6小GT3在LHCGR内化中的作用。从正常妇女（n = 19）和PCOS妇女（n = 17）取卵过程中收集的卵泡液中分离的颗粒细胞（GC）用于研究正常和PCOS患者之间LHCGR蛋白表达和活性的差异。LHCGR在PCOS患者胃癌中的表达上调PCOS GC中的LHCGR在功能上是活跃的，如在人促性腺激素（HCG）刺激后增加的cAMP产生所示。此外，ARF 6在PCOS患者的GC中高度表达，HCG刺激增加了活性ARF 6的浓度。ARF 6激活的抑制减弱了正常和PCOS GC中HCG诱导的LHCGR内化，表明PCOS GC中LHCGR内化没有改变。总之，LHCGR和ARF 6的表达和激活在PCOS妇女的GC中上调，但激动剂诱导的LHCGR内化的机制没有改变。(C)2016生殖保健有限公司由爱思唯尔有限公司出版。版权所有。
Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.