Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries.
Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries.
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DOI：
10.1093/molehr/gah066
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发表时间：
2004-07
影响因子：
4
通讯作者：
Hui-Wen Yen;A. Jakimiuk;I. Munir;D. Magoffin
中科院分区：
文献类型：
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作者：
Hui-Wen Yen;A. Jakimiuk;I. Munir;D. Magoffin
许多患有多囊卵巢综合征(PCOS)的女性体内胰岛素浓度升高可能是卵巢高雄激素血症的重要原因。本研究的目的是比较多囊卵巢和正常周期对照组的卵泡膜细胞和颗粒细胞中近端胰岛素信号分子的含量。取自11例多囊卵巢综合征患者和10例正常对照妇女的单个卵泡，卵泡直径3~7 mm。显微解剖每个卵泡的膜细胞和颗粒细胞。提取总蛋白，用免疫印迹法检测信号蛋白。PCOS组和对照组的卵泡膜细胞和颗粒细胞的胰岛素受体含量均无差异。PCOS膜细胞胰岛素受体底物(IRS)-1和-2增加(P<0.05)，IRS-4减少(P<；0.03)。颗粒细胞IRS-1、IRS-2、IRS-4无明显变化。在所有样品中均未检测到IRS-3。卵泡膜细胞和颗粒细胞的磷脂酰肌醇-3激酶催化亚基p110α或p110β无明显变化。这些数据显示了多囊卵巢膜细胞中IRS蛋白浓度的细胞特异性变化，这与胰岛素信号的夸大放大是一致的，这可能在卵巢高雄激素血症和膜层增生中发挥重要作用。
The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles (3-7 mm) were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased (P<0.05), but IRS-4 was decreased (P<0.03) in PCOS theca cells. There were no changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all samples. There were no changes in phosphatidyl inositol-3 kinase catalytic subunits p110alpha or p110beta in either theca or granulosa cells. These data demonstrate cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.