孕激素对乳腺癌细胞系MCF-7中硫酸酯酶和硫转移酶的影响

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。

Effects of progestins on slfatase and slfotransferase in hman beast cncer clls MCF-7

Objectives: Recent findings of the Women's Health Initiative (WHI)study have raised the concern that menopausal hormone replacement therapy with estrogen/medroxyprogesterone acetate (MPA) may enhance the risk of breast cancer when compared with estrogen given alone, indicating a need for studies on the role of progestins in contributing to breast cancer risk. Because increases in local estrogen production are closely involved in onset and growth of breast cancer, we investigated the effects of progestins on two estrogen-metabolizing enzymes, sulfates and sulfotransferase, in breast cancer cells MCF-7. Methods: The human hormone-dependent breast cancer cell lines MCF-7 were cultured with estradiol (E2) and progestins. The activity and mRNA levels of enzymes were determined by radiolabeled substrates and RT-PCR respectively. Results: Mdroxyprogesterone acetate (MPA) plus E2 (10-8 M) stimulated both the mRNA levels and activities of sulfatase (at 10-8-10-6 M) compared to E2 only. Progesterone also stimulated enzyme activity, but to a lower magnitude. Levonorgestrel, norethindrone, and dienogest showed no enzyme stimulation. Sulfotransferase were not affected by any of the progestogens tested. Conclusions: The present study suggested that different type of progestins exerts different actions on sulfates and sulfotransferase in breast cancer cells. Further studies are needed to elucidate whether MPA, a progestin currently used in HRT, leads to a higher risk of breast cancer development than other progestins via influencing the estrogen-metabolizing enzymes.Key wrds: hormone replacement therapy; breast cancer cells; progestin; estrogen-metabolizing enzyme; sulfatase; sulfotransferase