Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis.
Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis.
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DOI：
10.1186/1757-2215-7-21
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发表时间：
2014-02-13
影响因子：
4
通讯作者：
Duleba AJ
中科院分区：
文献类型：
--
作者：
Ortega I;Villanueva JA;Wong DH;Cress AB;Sokalska A;Stanley SD;Duleba AJ
多囊卵巢综合征（PCOS）的特征是卵巢增大、卵泡膜室增生和雄激素产生增加，这至少部分是由于参与类固醇生成的几个关键基因的过度表达。以前，我们的小组已经证明，辛伐他汀，3-羟基-3-甲基-戊二酰-CoA还原酶（HMG-CoA还原酶）的竞争性抑制剂，甲羟戊酸途径的限速步骤，减少大鼠卵泡膜间质细胞类固醇通过抑制Cyp 17 a1基因表达，雄激素生物合成途径的关键酶。最近，我们证明，白藜芦醇，丰富的红葡萄中的双黄酮类化合物，减少大鼠卵泡膜间质细胞类固醇的合成，这种抑制作用是通过独立的甲羟戊酸途径的机制介导的。本研究评估了辛伐他汀和白藜芦醇联合治疗对大鼠卵泡膜间质细胞类固醇合成的影响。从30日龄雌性大鼠分离的大鼠卵泡膜间质细胞在有或没有辛伐他汀（1 μM）和/或白藜芦醇（3-10 μM）的情况下培养长达48小时。通过定量真实的时间PCR评估类固醇生成酶基因表达，并通过液相色谱-质谱法测量类固醇水平。使用ANOVA和Tukey检验进行组间比较。白藜芦醇增强辛伐他汀对卵泡膜间质细胞雄烯二酮和雄酮产生的抑制作用。这种抑制作用与在白藜芦醇和辛伐他汀的组合存在下Cyp 17 a1 mRNA表达的深刻抑制相关。目前的研究结果表明，白藜芦醇加强辛伐他汀诱导的抑制作用卵泡膜间质细胞雄激素的生产，提高了PCOS的新的治疗方法的发展的可能性。
Polycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, hyperplastic theca compartment and increased androgen production due to, at least in part, excessive expression of several key genes involved in steroidogenesis. Previously, our group has demonstrated that simvastatin, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a rate-limiting step of the mevalonate pathway, reduces rat-theca interstitial cell steroidogenesis by inhibiting Cyp17a1 gene expression, the key enzyme of the androgen biosynthesis pathway. Recently, we demonstrated that resveratrol, a bioflavonoid abundant in red grapes, decreases rat theca-interstitial cell steroidogenesis and this suppressive effect is mediated through mechanisms independent of the mevalonate pathway. The present study evaluated the effect of combining simvastatin and resveratrol treatments on rat theca-interstitial cell steroidogenesis. Rat theca-interstitial cells isolated from 30 day-old female rats were cultured for up to 48 h with or without simvastatin (1 μM) and/or resveratrol (3-10 μM). Steroidogenic enzymes gene expression was evaluated by quantitative real time PCR and steroid levels were measured by liquid chromatography-mass spectrometry. Comparisons between groups were performed using ANOVA and Tukey test. Resveratrol potentiated inhibitory effects of simvastatin on androstenedione and androsterone production in theca-interstitial cells. This suppressive effect correlated with profound inhibition in Cyp17a1 mRNA expression in the presence of a combination of resveratrol and simvastatin. The present findings indicate that resveratrol potentiates the simvastatin-induced inhibitory effect on theca-interstitial cell androgen production, raising the possibility of development of novel treatments of PCOS.
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影响因子：
27.4
作者：
Gao Xuzhu;Komai-Koma, Mousa;Xu, Damo
通讯作者：
Xu, Damo
影响因子：
4.8
作者：
Parrott, JA;Skinner, MK
通讯作者：
Skinner, MK
影响因子：
5.8
作者：
Jakimiuk, AJ;Weitsman, SR;Magoffin, DA
通讯作者：
Magoffin, DA
DOI：
10.1016/j.bbrc.2008.06.113
发表时间：
2008-09-12
影响因子：
3.1
作者：
Do, Gyeong-Min;Kwon, Eun-Young;Choi, Myung-Sook
通讯作者：
Choi, Myung-Sook
DOI：
10.1016/j.jpba.2009.03.026
发表时间：
2010-01-20
影响因子：
3.4
作者：
Emilia Juan, M.;Maijo, Monica;Planas, Joana M.
通讯作者：
Planas, Joana M.