Eryxin通过抑制芳香化酶表达调控雌激素生物合成

Eryxin inhibits estrogen biosynthesis by suppression of aromatase

雌激素水平与女性生理及心理健康密切相关,为探讨eryxin对雌激素生物合成的影响,采用Am-blue法检测eryxin对人卵巢颗粒细胞KGN细胞增殖的影响,磁微粒分离酶联免疫法检测雌二醇的合成,Western blotting检测KGN细胞芳香化酶蛋白表达水平,RT-qPCR检测KGN细胞芳香化酶基因及其启动子PromoterⅡ表达水平.结果显示,在1-150μg/mL范围内eryxin对细胞增殖没有影响,但是可以显著抑制KGN细胞中雌二醇的合成,且具有剂量依赖性;eryxin对芳香化酶过表达的HEK-293A细胞中雌二醇的合成没有影响;eryxin显著下调芳香化酶的mRNA和蛋白质表达水平,抑制芳香化酶启动子PromoterⅡ表达;降低eryxin中蛋白质含量可显著削弱其抑制雌激素合成的活性.本研究表明eryxin抑制人卵巢颗粒细胞雌激素的合成是通过其抑制芳香化酶mRNA及蛋白表达来实现的,结果可为进一步发现新型抗雌激素生物合成药物治疗相关相关疾病奠定基础.

Estrogen levels are a major factor affecting the physiological and mental health of women.The effect of eryxin on estrogen biosynthesis was investigated.The Am-blue method was used to detect the effect of eryxin on the proliferation of human ovarian granulosa(KGN) cells.The effects of eryxin on estrogen biosynthesis in KGN cells and aromataseove rexpressing HEK-293 A(HEK-293 Aaro) cells were examined by enzyme-linked immunosorbent assay(ELISA).The expression of aromatase protein in KGN cells were detected by Western blotting.We also examined the expression of aromatase gene and Promoter Ⅱ by RT-qRCR.The results showed that 1-150 μg/mL of eryxin had no effect on cell proliferation but it potently inhibited the biosynthesis of 17β-estradiol in KGN cells in a dose-dependent manner;it had no effect on the catalytic activity of aromatase in HEK-293 Aaro cells.Eryxin significantly down-regulated the mRNA and protein expression of aromatase protein by decreasing the expression of aromatase Promoter Ⅱ.Boiling and enzymolysis significantly attenuated the inhibitory effect of eryxin on estrogen biosynthesis in KGN cells.Eryxin suppressed estrogen biosynthesis in KGN cells by the inhibition of aromatase expression,and it warrants further investigation as a candidate for the treatment of estrogen-related diseases.