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目的WHI的研究结果发现,与单用雌激素比较,雌孕激素合用的激素替代治疗可能增加了乳腺癌发生的危险性。从而使得人们对于孕激素的作用引起关注。由于局部雌激素浓度的增高与乳腺癌的发生和发展密切相关,本研究旨在探讨乳腺癌细胞系中孕激素对两种雌激素代谢酶,硫酸酯酶和硫转移酶的影响。方法将人乳腺癌细胞系MCF-7在加入了雌二醇和孕激素的培养液中进行培养。用同位素标记的底物和RT—PCR技术分别测定硫酸酯酶和硫转移酶的活性和mRNA表达水平。结果与单用雌二醇相比,安宫黄体酮/雌二醇合用刺激硫酸酯酶,使其活性和mRNA表达水平均显著升高,差异具有显著性。黄体酮表现了类似的作用,但刺激幅度低于安宫黄体酮。左炔诺孕酮,炔诺酮和地诺孕酮无刺激作用。五种孕激素对硫转移酶的活性和mRNA表达影响。结论本研究表明,乳腺癌细胞中,不同类型的孕激素对雌激素代谢酶具有不同的作用。对于目前激素替代治疗中常用的孕激素安宫黄体酮是否可以通过影响雌激素代谢酶的活性而增加乳腺癌的危险性,尚有待于更深入的研究。
Purpose WHI’s study found that hormone replacement therapy in combination with estrogen and progestogen may increase the risk of breast cancer compared with estrogen alone. So that people’s role for progesterone cause concern. As the local estrogen concentration is closely related to the occurrence and development of breast cancer, this study aimed to investigate the effects of progestins on two estrogen metabolizing enzymes, sulfatase and S-transferase in breast cancer cell lines. Methods The human breast cancer cell line MCF-7 was cultured in culture medium containing estradiol and progesterone. The activities of sulfatase and S-transferase and mRNA expression levels were determined by isotope labeled substrate and RT-PCR respectively. Results Compared with the single administration of estradiol, Andong progesterone combined with estradiol stimulate the activity of sulfatase and its mRNA expression levels were significantly increased, the difference was significant. Progesterone showed a similar effect, but the stimulus was lower than that of progesterone. Levonorgestrel, norethindrone and dronedorone had no stimulatory effects. Effects of five progestins on the activity of S transferase and mRNA expression. Conclusions This study shows that different types of progestins have different effects on estrogen metabolizing enzymes in breast cancer cells. For the current hormone replacement therapy progesterone and progesterone progesterone progesterone can affect the activity of estrogen metabolism by increasing the risk of breast cancer remains to be further studied.