Pasqualini J R
Hormones and Cancer Research Unit, Institut de Puériculture, 26 Blvd. Brune, Paris 75014, France.
Maturitas. 2003 Dec 10;46 Suppl 1:S45-54. doi: 10.1016/j.maturitas.2003.09.018.
There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E2) from circulating precursors. Two principal pathways are implicated in the final steps of E2 formation in breast cancer tissue: the 'aromatase pathway' that transforms androgens into estrogens and the 'sulfatase pathway' that converts estrone sulfate (E1S) into estrone (E1) via estrone sulfatase. The final step is the conversion of weak E1 to potent biologically active E2 via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. One of the possible means of blocking E2 effects in breast cancer is to use anti-estrogens, which act by binding to the estrogen receptor (ER). Another option is to block E2 using anti-enzymes (anti-sulfatase, anti-aromatase, or anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD). Various progestins (e.g. promegestone, nomegestrol acetate, medrogestone, 17-deacetyl norgestimate, dydrogesterone and its 20-dihydro derivative), as well as tibolone and its metabolites, have been shown to inhibit estrone sulfatase and 17beta-hydroxysteroid dehydrogenase. Some progestins and tibolone can also stimulate sulfotransferase activity. These various progestins may therefore provide a new option for the treatment of breast cancer.
有大量证据表明，乳腺癌组织含有所有负责从循环前体物质中局部生物合成雌二醇（E2）的酶。在乳腺癌组织中，E2形成的最后步骤涉及两条主要途径：将雄激素转化为雌激素的“芳香化酶途径”和通过硫酸酯酶将硫酸雌酮（E1S）转化为雌酮（E1）的“硫酸酯酶途径”。最后一步是通过1型还原型17β-羟基类固醇脱氢酶的活性将弱活性的E1转化为具有强生物活性的E2。同样确定的是，将雌激素转化为其硫酸盐的类固醇硫酸转移酶存在于乳腺癌组织中。在乳腺癌中阻断E2作用的一种可能方法是使用抗雌激素，其通过与雌激素受体（ER）结合而起作用。另一种选择是使用抗酶（抗硫酸酯酶、抗芳香化酶或抗17β-羟基类固醇脱氢酶（17β-HSD））来阻断E2。各种孕激素（如普美孕酮、醋酸诺美孕酮、甲羟孕酮、17-去乙酰诺孕酯、地屈孕酮及其20-二氢衍生物）以及替勃龙及其代谢产物已被证明可抑制硫酸雌酮和17β-羟基类固醇脱氢酶。一些孕激素和替勃龙还可刺激硫酸转移酶活性。因此，这些各种孕激素可能为乳腺癌的治疗提供新的选择。
