The post-menopausal ovary displays a unique pattern of steroidogenic enzyme expression
The post-menopausal ovary displays a unique pattern of steroidogenic enzyme expression
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DOI：
10.1093/humrep/dei373
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发表时间：
2006-01-01
影响因子：
6.1
通讯作者：
Carr, BR
中科院分区：
文献类型：
--
作者：
Havelock, JC;Rainey, WE;Carr, BR
背景技术背景：虽然绝经导致环类固醇产生的损失，但有证据表明卵巢雄激素的产生持续减少。为了继续合成卵巢雄激素，雄激素生物合成所必需的类固醇生成酶必须存在。很少有研究选择性地分析了绝经后卵巢（PMO）中存在的一些类固醇生成酶，并且从未对这一问题进行过全面的研究。方法：从PMO、绝经前卵巢基质、黄体（CL）、卵泡、胎盘和子宫肌层中获得RNA和蛋白。寡核苷酸芯片分析比较PMO与绝经前卵巢间质的基因表达谱。对LH/HCG受体（LHCGR）、类固醇生成急性调节（星星）、胆固醇侧链裂解（CYP 11 A）、3 β-羟基类固醇脱氢酶I型（HSD 3B 1）和II型（HSD 3B 2，3bHSD）、17 α-羟化酶（CYP 17）、细胞色素b5（CytB 5）和芳香酶（CYP 19）进行实时RT-PCR。对星星、CYP 11 A、CYP 17和3 β HSD进行蛋白质印迹分析。结果：PMO和绝经前卵巢间质具有相似的类固醇生成酶表达模式。PMO有持久的，但减少，LHCGR和大多数类固醇生成酶的水平。与CL相比，PMO中CYP 19和HSD 3B 2 mRNA大大降低（分别降低50倍和2000倍）。Western分析未检测到HSD 3B 2。结论：本研究支持PMO保留了一些类固醇生成能力的观点。然而，基于类固醇生成酶表达，PMO具有独特的类固醇生成酶表达模式，其有利于Delta（5）类固醇形成而不是Delta（4）类固醇形成。
BACKGROUND: While menopause results in the loss of cyclic steroid production, evidence exists for persistent, albeit reduced, ovarian androgen production. In order to continue to synthesize ovarian androgens, the steroidogenic enzymes necessary for androgen biosynthesis must be present. Few studies have selectively analysed some of the steroidogenic enzymes present in the post-menopausal ovary (PMO), and a comprehensive study of this matter has never been undertaken. METHODS: RNA and protein were obtained from PMO, pre-menopausal ovarian stroma, corpora lutea (CL), ovarian follicles, placenta, and myometrium. Oligonucleotide microarray analysis was performed to compare the gene expression profiles of PMO with pre-menopausal ovarian stroma. Real-time RT-PCR was performed for LH/HCG receptor (LHCGR), steroidogenic acute regulatory (StAR), cholesterol side-chain cleavage (CYP11A), 3 beta-hydroxysteroid dehydrogenase type I (HSD3B1) and type II (HSD3B2, 3bHSD), 17 alpha-hydroxylase (CYP17), cytochrome b5 (CytB5), and aromatase (CYP19). Western blot analysis was performed for StAR, CYP11A, CYP17,and 3 beta HSD. RESULTS: The PMO and pre-menopausal ovarian stroma had a similar pattern of steroidogenic enzyme expression. The PMO had persistent, but reduced, levels of LHCGR and most steroidogenic enzymes. CYP19 and HSD3B2 mRNA were greatly reduced in PMO in comparison with CL (50-fold and 2000-fold less respectively). HSD3B2 was not detectable in PMO by western analysis. CONCLUSIONS: This study supports the idea that the PMO retains some steroidogenic capacity. However, based on steroidogenic enzyme expression, the PMO has a unique pattern of steroidogenic enzyme expression that favors Delta(5) steroid formation over Delta(4) steroid formation.