PDF(Pubmed)
Abstract：
Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs.
摘要：
雄激素过量是多囊卵巢综合征（PCOS）几种临床表型的关键特征。然而,FSH受体(FSHR)和芳香化酶(CYP19A1)活性对生理内分泌刺激的反应在PCOS的发病机制中起关键作用。初步数据表明，肌醇（myo-Ins）和D-Chiro-肌醇（D-Chiro-Ins）可能会重新激活CYP19A1活性。我们在暴露于连续光照10周的CD1小鼠中诱导的小鼠PCOS的实验模型中研究了Theca（TC）和颗粒细胞（GC）的类固醇生成途径。不同组合的myo-Ins和D-Chiro-Ins治疗对Fshr表达的影响,雄激素,通过实时PCR分析分离的TC和GC以及从健康和PCOS小鼠分离的卵巢中的雌激素酶。Myo-Ins和D-Chiro-Ins,在药理和生理浓度下，比例为40:1，正调节TCs的类固醇生成活性以及GCs中Cyp19a1和Fshr的表达。此外，在体内，肌醇（40：1比例）显着增加Cyp19a1和Fshr。基因表达的这些变化反映在治疗动物血清中激素水平的改变上。40：1配方中的Myo-Ins和D-Chiro-Ins通过上调芳香化酶和FSHR水平，同时下调TC产生的雄激素过剩，有效地拯救了PCOS特征。
