Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of women using a levonorgestrel-releasing intrauterine system
Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of women using a levonorgestrel-releasing intrauterine system
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DOI：
10.1093/humrep/13.5.1210
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发表时间：
1998-05-01
影响因子：
6.1
通讯作者：
Glasier, AF
中科院分区：
文献类型：
--
作者：
Critchley, HOD;Wang, H;Glasier, AF
本研究检查了14名正常妇女在插入左炔诺孕酮宫内释放系统（LNG-IUS）之前的子宫内膜组织，此后纵向长达12个月后插入。免疫组化检测孕激素受体（PR）亚型A + B、雌激素受体（ER）和前列腺素脱氢酶（PGDH）。分别用抗PR B亚型和PR亚型A + B的抗孕酮受体抗体检测PR亚型的定位，并测定PGDH活性。在持续宫内LNG输送的情况下，ER和PRA+B和PR亚型B在腺体和间质中显著下调。有一个明显的增加，PRA免疫反应在子宫内膜腺体之间6和12个月后插入。与PR的两种亚型的下调一致的是，在LNG-IUS插入后腺体PGDH免疫染色减少，并且PGDH活性通过体外过量底物的代谢来测量。此外，PGDH活性（已知位于腺体中）在插入后12个月显著增加（P < 0.05），与此时观察到的腺体PRA+B免疫反应性增加一致。由于LNG-IUS如此强烈地抑制PRB，PRA可能是介导子宫内膜中长期LNG作用的亚型，PRB是两种亚型中受抑制程度更高的亚型，并且只有PRA随着PGDH活性沿着升高。暴露于高浓度局部LNG后，正常子宫内膜形态和功能的改变，例如正常性类固醇受体表达的扰动，可能在与LNG-IUS相关的出血性疾病的病因学中发挥作用，需要进一步阐明与出血问题机制相关的局部子宫介质。
This study has examined endometrial tissue in 14 normal women prior to insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) and thereafter longitudinally for up to 12 months post-insertion. The specific endpoints examined by immunohistochemistry were progesterone receptor (PR) subtypes A + B, oestrogen receptor (ER) and prostaglandin dehydrogenase (PGDH), Two antiprogesterone receptor antibodies, one specific to PRB subtype and the other to PR subtype A + B, were employed to examine the localization of both PR isoforms, The activity of PGDH, a progesterone dependent enzyme, was also measured. ER and PRA+B and PR subtype B were significantly down-regulated in glands and stroma in the presence of continuous intrauterine LNG delivery. There was an apparent increase in PRA immunoreactivity in endometrial glands between 6 and 12 months post-insertion. Consistent with down-regulation of both isoforms of PR was reduced glandular PGDH immunostaining following LNG-IUS insertion, and PGDH activity las measured by metabolism of excess substrate in vitro). Furthermore, PGDH activity, known to be localized in the glands, significantly increased (P < 0.05) at 12 months post-insertion, coinciding with the observed increase in glandular PRA+B immunoreactivity at this time. Since the LNG-IUS suppresses the PRB so strongly, PRA is likely to be the subtype that mediates long term LNG action in the endometrium, PRB is the more suppressed of the two subtypes, and only PRA rises along with PGDH activity. Alterations to normal endometrial morphology and function, e.g. perturbation of normal sex steroid receptor expression, following exposure to high concentrations of local LNG, may play a role in the aetiology of bleeding disorders associated with the LNG-IUS, Further elucidation of local uterine mediators involved in the mechanism of bleeding problems is required.