Retinoid receptors in the human endometrium and its disorders: a possible modulator of 17 beta-hydroxysteroid dehydrogenase.
Retinoid receptors in the human endometrium and its disorders: a possible modulator of 17 beta-hydroxysteroid dehydrogenase.
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DOI：
10.1210/jcem.86.6.7546
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发表时间：
2001-06
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影响因子：
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通讯作者：
K Ito;T. Suzuki;T. Moriya;H. Utsunomiya;A. Sugawara;R. Konno;S. Sato;H. Sasano
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文献类型：
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作者：
K Ito;T. Suzuki;T. Moriya;H. Utsunomiya;A. Sugawara;R. Konno;S. Sato;H. Sasano
维甲酸类化合物最近被提出用于调节各种性激素依赖型肿瘤的雌激素活性，但在人类子宫内膜疾病中的研究很少。因此，在这项研究中，我们首先检测了维甲酸受体α、β和伽马以及维甲酸X受体(RXR)在20例正常周期子宫内膜、34例子宫内膜增生症和46例子宫内膜样腺癌中的免疫定位。然后，我们将这些发现与其他临床病理参数相关联，特别是在维甲酸受体亚型与类固醇激素受体、17β-羟基类固醇脱氢酶(17β-HSD)和芳香酶状态之间的相关性。然后，我们还利用Northern印迹分析检测了维甲酸对子宫内膜癌细胞系中17β-HSD 2型表达的影响，以探讨维甲酸在子宫内膜原位雌激素代谢中的可能作用。在所检测的6种维甲酸受体中，RXR-γ仅在分泌期子宫内膜上皮细胞中检测到，而在增生期则不表达，这与17β-HSD 2型免疫定位密切相关。在子宫内膜样腺癌中，17β-HSD 2型表达与RXRγ标记指数(LI)呈正相关(P<0.001)，与孕激素受体LI呈正相关(r=0.501，P=0.003)。RXRγLI与年龄呈显著负相关(r=0.449，P=0.015)。受体的LIS与其他临床病理参数，包括免疫组织化学检测的瘤内芳香酶状态之间没有统计学意义的相关性。在子宫内膜癌细胞株RL95-2中，维甲酸以时间和剂量依赖的方式显著增加17β-HSD 2型信使RNA的水平。这些结果都表明，维甲酸可能通过RXR-γ刺激17β-HSD 2型的表达，参与调节正常和肿瘤人子宫内膜雌激素的原位代谢。
Retinoids have recently been proposed to modulate estrogenic actions in various sex steroid-dependent neoplasms, but little has been studied in human endometrial disorders. Therefore, in this study, we first examined the immunolocalization of retinoic acid receptor alpha, beta, and gamma, and retinoid X receptor (RXR) alpha, beta, and gamma in 20 normal cycling human endometria, 34 endometrial hyperplasia, and 46 endometrioid endometrial adenocarcinomas. We then correlated these findings with other clinicopathological parameters, especially in the correlation between retinoid receptor subtypes and the status of steroid hormone receptors, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and aromatase. We also then examined the effects of retinoic acid on the expression of 17 beta-HSD type 2 in cell lines derived from endometrial carcinoma using Northern blotting analysis to examine the possible roles of retinoids in in situ endometrial estrogen metabolism. Among these six retinoid receptors examined, RXR gamma immunoreactivity was exclusively detected in the epithelial cells of the secretory phase endometrium but not of the proliferative phase, which was well correlated with 17 beta-HSD type 2 immunolocalization. However, in endometrial hyperplasia, RXR gamma was not correlated with 17 beta-HSD type 2. In endometrioid endometrial adenocarcinoma, there was a statistically significant correlation between 17 beta-HSD type 2 immunoreactivity and RXR gamma labeling index (LI) (P < 0.001) and between RXR gamma LI and progesterone receptor LI (r = 0.501, P = 0.003). A significant inverse correlation was also detected between RXR gamma LI and patient age (r = 0.449, P = 0.015). No statistically significant correlation was obtained between LIs of receptors and other clinicopathological parameters including the status of intratumoral aromatase examined by immunohistochemistry. In the endometrial carcinoma cell line, RL95-2, retinoic acid markedly increased the level of 17 beta-HSD type 2 messenger RNA in a time- and dose-dependent manner. These results all suggest that retinoic acids may be involved in modulation of in situ estrogen metabolism in both normal and neoplastic human endometrium possibly through RXR gamma by stimulating the expression of 17 beta-HSD type 2.