Endometrial and Endometriotic Concentrations of Estrone and Estradiol Are Determined by Local Metabolism Rather than Circulating Levels
Endometrial and Endometriotic Concentrations of Estrone and Estradiol Are Determined by Local Metabolism Rather than Circulating Levels
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DOI：
10.1210/jc.2012-1154
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发表时间：
2012-11-01
影响因子：
5.8
通讯作者：
Poutanen, Matti
中科院分区：
文献类型：
--
作者：
Huhtinen, Kaisa;Desai, Reena;Poutanen, Matti
内容：雌激素的异常合成和代谢被认为可增加子宫内膜异位症局部雌二醇（E2）浓度，从而促进病变的生长。然而，子宫内膜和不同类型的子宫内膜异位症病变内的组织雌激素浓度尚未被描述。目的：本研究的目的是评估子宫内膜和不同类型的子宫内膜异位症病变中的局部E2和雌酮（E1）浓度，并将它们与雌激素代谢酶的表达相关联。患者：子宫内膜异位症患者（n = 60）和健康对照者（n = 16）参加了这项研究。主要结果测量：我们测量了血清和组织中E2和E1的浓度以及雌激素代谢酶的mRNA表达。子宫内膜或子宫内膜异位症组织内E2浓度并不反映相应的血清水平。在增殖期，子宫内膜E2浓度比血清中高5 - 8倍，而在分泌期，E2浓度约为血清中的一半。因此，在子宫内膜中观察到的E2/E1比值在增殖期明显高于分泌期。在子宫内膜异位症病变，E2水平占主导地位的E1在整个月经周期。在羟基类固醇（17 β）脱氢酶（HSD 17 B）的酶分析，HSD 17 B2与E2浓度在子宫内膜呈负相关，和HSD 17 B6强烈表达，特别是在深部lesions.Conclusions：子宫内膜或子宫内膜异位组织E2浓度的积极调节局部雌激素代谢的组织。因此，抑制局部E2的合成是一种有效的，新的方法，以减少局部E2依赖性的增生组织的生长。（临床内分泌代谢杂志97：4228-4235，2012）
Context: Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described.Objective: The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes.Patients: Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study.Main Outcome Measures: We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes.Results: Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, whereas in the secretory phase the E2 concentration was about half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was observed in the endometrium at the proliferative phase compared with the secretory phase. In the endometriosis lesions, E2 levels were predominating over those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17 beta) dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the E2 concentration in the endometrium, and HSD17B6 was strongly expressed, especially in the deep lesions.Conclusions: Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue. (J Clin Endocrinol Metab 97: 4228-4235, 2012)