Delvoux Bert, Groothuis Patrick, D'Hooghe Thomas, Kyama Cleophas, Dunselman Gerard, Romano Andrea
GROW, School for Oncology and Developmental Biology, University Maastricht, and Department of Obstetrics and Gynecology, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands.
J Clin Endocrinol Metab. 2009 Mar;94(3):876-83. doi: 10.1210/jc.2008-2218. Epub 2008 Dec 16.
substantial evidence suggests that the expression of steroid metabolizing enzymes in endometriosis is altered, turning the ectopic endometrium into a source of 17beta-estradiol. However, whether these differences result in a net increase in local 17beta-estradiol production/activity has not been shown.
The activities of the most important steroidogenic enzymes synthesizing and inactivating 17beta-estradiol were determined by HPLC in matched eutopic and ectopic tissue from patients with endometriosis (n = 14) and in endometrium from controls (n = 20).
Aromatase activity is negligible in the ectopic endometrium, whereas the activity of estrogen sulfatase is high though not different between ectopic, eutopic and control endometrium. The activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) converting estrone into 17beta-estradiol is higher in the ectopic compared to the eutopic endometrium in patients. The activity of 17beta-HSDs converting 17beta-estradiol back to estrone is significantly lower in the ectopic compared to the eutopic endometrium of both patients and controls. To evaluate the net metabolic capacity of tissues to synthesize 17beta-estradiol, we calculated the activity ratio between 17beta-HSDs synthesizing versus 17beta-HSDs inactivating 17beta-estradiol. This ratio is significantly higher in the ectopic compared to the eutopic endometrium of patients and controls, indicating a high synthesis of 17beta-estradiol in the ectopic locations. This is further supported by the elevated mRNA levels of the estrogen-responsive gene TFF1 in all ectopic compared to eutopic endometria.
Endometriotic lesions have higher production of 17beta-estradiol than the eutopic endometrium of patients and controls. This is mostly the result of impaired metabolism.
大量证据表明，子宫内膜异位症中甾体代谢酶的表达发生改变，使异位子宫内膜成为17β-雌二醇的来源。然而，这些差异是否导致局部17β-雌二醇产生/活性的净增加尚未得到证实。
采用高效液相色谱法测定了14例子宫内膜异位症患者的异位和在位内膜以及20例对照者子宫内膜中合成和灭活17β-雌二醇的最重要甾体生成酶的活性。
异位子宫内膜中的芳香化酶活性可忽略不计，而硫酸酯酶活性较高，尽管异位、在位和对照子宫内膜之间无差异。与在位子宫内膜相比，患者异位子宫内膜中使雌酮转化为17β-雌二醇的17β-羟基类固醇脱氢酶（17β-HSDs）活性更高。与患者和对照者的在位子宫内膜相比，异位子宫内膜中使17β-雌二醇转化回雌酮的17β-HSDs活性显著降低。为了评估组织合成17β-雌二醇的净代谢能力，我们计算了合成17β-雌二醇的17β-HSDs与灭活17β-雌二醇的17β-HSDs之间的活性比值。与患者和对照者的在位子宫内膜相比，该比值在异位子宫内膜中显著更高，表明异位部位17β-雌二醇合成量较高。与在位子宫内膜相比，所有异位子宫内膜中雌激素反应基因TFF1的mRNA水平升高进一步支持了这一点。
子宫内膜异位症病灶产生的17β-雌二醇高于患者和对照者的在位子宫内膜。这主要是代谢受损的结果。
