核受体激动剂对人卵巢颗粒细胞和乳腺癌MCF-7细胞芳香化酶的调节作用

Nuclear receptor agonist regulating aromatase activity in human ovarian granulosa and breast cancer MCF-7 cells

目的 :探讨各种核受体包括过氧化酶体增生物激活受体 γ(PPARγ)和 α(PPARα)、维甲酸受体 (RAR)、维甲类 X受体 (RXR)、维生素 D受体 (VDR)、甲状腺素受体 (TR)和糖皮质激素受体 (GR)的激动剂对人卵巢颗粒细胞和乳腺癌 MCF- 7细胞芳香化酶活性的调节作用。 方法 :测定人卵巢颗粒细胞和 MCF- 7细胞在上述各种核受体激动剂处理前后芳香化酶活性的变化和细胞色素 P4 5 0芳香化酶 (P4 5 0 arom) m RNA的表达水平。结果 :(1) PPARγ和 RXR激动剂均能显著抑制人卵巢颗粒细胞芳香化酶活性 ,两者结合使用抑制作用更进一步增强 ,并且伴有 P4 5 0 arom m RNA水平下降 ;(2 ) RAR和 RXR激动剂合用能显著刺激乳腺癌 MCF- 7细胞芳香化酶活性 ,并使 P4 5 0 arom m RNA表达水平升高。 结论 :人卵巢颗粒细胞和乳腺癌MCF-

Objective:To investigate the regulatory effect of nuclear receptors including peroxisome proliferator activated receptorγ (PPARγ) and α(PPARα),retinoic acid receptor(RAR),retinoid X receptor (RXR),vitamin D receptor (VDR),thyroxin receptor (TR) and glucocorticoid receptor (GR) agonist on aromatase activity in human ovarian granulosa and breast cancer MCF 7 cells.Methods:The human ovarian granulosa and breast cancer MCF 7 cells were treated with various nuclear receptor agonist mentioned above for 2 d and then aromatase activity was determined by measuring the H 2O release upon the conversion of [1β 3H] and rostenedion to estrone (E 1).Results:(1) PPARγ or RXR agonist alone decreased aromatase activity in cultured granulosa cells,while combined treatment with both agonist caused a much greater reduction in aromatase activity and associated with comparable changes in the P450arom mRNA levels based on RT PCR;(2) Combined treatment with both RXR agonist and RAR agonist increased aromatase activity and P450arom mRNA level in MCF 7 cells.Conclusion:aromatase activity is regulated by different nuclear receptor agonist in human ovarian granulosa and breast cancer MCF 7 cells.