Institute of Reproductive and Developmental Biology, Imperial College London, London, UK.
Hum Reprod. 2013 Nov;28(11):3086-92. doi: 10.1093/humrep/det352. Epub 2013 Sep 5.
Does the expression of LHCG receptor (LHCGR) protein and key enzymes in the androgen biosynthetic pathway differ in normal human versus polycystic ovarian tissue?
LHCGR and 17α-hydroxylase/17-20-lyase (CYP17A1) protein levels are increased in polycystic ovaries (PCOs).
The predominant source of excess androgen secretion in women with polycystic ovary syndrome (PCOS) is ovarian theca cells but few studies have directly assessed the presence and abundance of protein for key molecules involved in androgen production by theca, including LHCGR and the rate-limiting enzyme in androgen production, CYP17A1.
STUDY DESIGN, SIZE, DURATION: This is a laboratory-based, cross-sectional study comparing protein expression of key molecules in the androgen biosynthetic pathway in archived ovarian tissue from women with normal ovaries (n = 10) with those with PCOs (n = 16).
PARTICIPANTS/MATERIALS, SETTING, METHODS: A quantitative morphometric study was performed using sections of archived human ovaries (n = 26) previously characterized as normal or polycystic. The distribution and abundance of LHCGR, CYP17A1, 3β-hydroxysteroid dehydrogenase type 2 (3βHSDII) and 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) proteins were evaluated by immunohistochemistry and quantified.
A higher proportion of theca cells from anovulatory PCO expressed LHCGR protein when compared with control ovaries (P = 0.01). A significant increase in the intensity of immunostaining for CYP17A1 was identified in antral follicles in sections of PCO compared with ovaries from normal women (P = 0.04).
LIMITATIONS, REASONS FOR CAUTION: As the study used formalin-fixed ovarian tissue sections, it was not possible to carry out studies 'in vitro' using the same ovarian tissues in order to also demonstrate increased functional activity of LHCGR and CYP17A1.
The data are in keeping with the results of previous studies in isolated theca cells and support the notion of an intrinsic abnormality of theca cell androgen production in women with PCOS.
STUDY FUNDING/COMPETING INTEREST(S): The research was supported by a Programme Grant, G0802782, from the Medical Research Council (MRC) UK and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. F.V.C was supported by Capes Foundation (Brazilian Ministry of Education). The authors have no conflicts of interest to disclose.
正常人和多囊卵巢组织中黄体生成素受体（LHCGR）蛋白和雄激素生物合成途径中的关键酶的表达是否不同？
多囊卵巢（PCO）中的 LHCGR 和 17α-羟化酶/17-20-裂合酶（CYP17A1）蛋白水平增加。
多囊卵巢综合征（PCOS）妇女中过多雄激素分泌的主要来源是卵巢间质细胞，但很少有研究直接评估与间质细胞雄激素产生相关的关键分子的存在和丰度，包括 LHCGR 和雄激素产生的限速酶，CYP17A1。
研究设计、大小和持续时间：这是一项基于实验室的横断面研究，比较了存档卵巢组织中雄激素生物合成途径中关键分子的蛋白表达，这些组织来自于 10 名正常卵巢（n=10）和 16 名多囊卵巢（PCO）患者。
参与者/材料、设置、方法：对先前被描述为正常或多囊的存档人类卵巢切片（n=26）进行了定量形态计量学研究。通过免疫组织化学评估 LHCGR、CYP17A1、3β-羟甾脱氢酶 2 型（3βHSDII）和 17β-羟甾脱氢酶 5 型（17βHSD5）蛋白的分布和丰度，并进行量化。
与对照组卵巢相比，无排卵性 PCO 的间质细胞中 LHCGR 蛋白的表达比例更高（P=0.01）。与正常女性卵巢相比，PCO 组织切片中发现 CYP17A1 免疫染色强度显著增加（P=0.04）。
局限性、谨慎的原因：由于研究使用了福尔马林固定的卵巢组织切片，因此无法使用相同的卵巢组织进行“体外”研究，以证明 LHCGR 和 CYP17A1 的功能活性增加。
这些数据与以前在分离的间质细胞中的研究结果一致，并支持 PCOS 妇女的间质细胞雄激素产生内在异常的观点。
研究资金/竞争利益：该研究得到了英国医学研究理事会（MRC）G0802782 计划拨款和帝国理工学院医疗保健 NHS 信托基金和帝国理工学院伦敦的国家卫生研究院（NIHR）生物医学研究中心的支持。F.V.C 得到了巴西教育部 Capes 基金会的支持。作者没有利益冲突需要披露。
