Marti Nesa, Bouchoucha Nadia, Sauter Kay-Sara, Flück Christa E
Division of Pediatric Endocrinology, Department of Pediatrics and Department of Clinical Research, University of Bern, Bern, Switzerland.
Graduate School of Bern, University of Bern, Bern, Switzerland.
PLoS One. 2017 Mar 21;12(3):e0174224. doi: 10.1371/journal.pone.0174224. eCollection 2017.
Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive effects on the human metabolism as caloric restriction. Recently, positive effects of resveratrol on steroid biosynthesis in cell systems and in humans suffering from polycystic ovary syndrome have also been reported, but the exact mechanism of this action remains unknown. Sirtuins seem targeted by resveratrol to mediate its action on energy homeostasis. In this study, we investigated the mechanisms of action of resveratrol on steroidogenesis in human adrenal H295R cells. Resveratrol was found to inhibit protein expression and enzyme activities of CYP17 and CYP21. It did not alter CYP17 and CYP21 mRNA expression, nor protein degradation. Only SIRT3 mRNA expression was found to be altered by resveratrol, but SIRT1, 3 and 5 overexpression did not result in a change in the steroid profile of H295R cells, indicating that resveratrol may not engage sirtuins to modulate steroid production. Previous studies showed that starvation leads to a hyperandrogenic steroid profile in H295R cells through inhibition of PKB/Akt signaling, and that resveratrol inhibits steroidogenesis of rat ovarian theca cells via the PKB/Akt pathway. Therefore, the effect of resveratrol on PKB/Akt signaling was tested in H295R cells and was found to be decreased under starvation growth conditions, but not under normal growth conditions. Overall, these properties of action together with recent clinical findings make resveratrol a candidate for the treatment of hyperandrogenic disorders such as PCOS.
白藜芦醇是一种在葡萄中发现的天然化合物，因其对衰老具有潜在的保护作用而备受关注。据报道，它对人体新陈代谢的积极作用与热量限制相似。最近，白藜芦醇对细胞系统和多囊卵巢综合征患者类固醇生物合成的积极作用也有报道，但其具体作用机制尚不清楚。白藜芦醇似乎通过靶向沉默调节蛋白来介导其对能量稳态的作用。在本研究中，我们研究了白藜芦醇对人肾上腺H295R细胞类固醇生成的作用机制。发现白藜芦醇可抑制CYP17和CYP21的蛋白表达和酶活性。它不会改变CYP17和CYP21的mRNA表达，也不会影响蛋白质降解。仅发现白藜芦醇会改变SIRT3的mRNA表达，但SIRT1、3和5的过表达并未导致H295R细胞类固醇谱的变化，这表明白藜芦醇可能不会通过沉默调节蛋白来调节类固醇生成。先前的研究表明，饥饿通过抑制PKB/Akt信号通路导致H295R细胞出现高雄激素性类固醇谱，并且白藜芦醇通过PKB/Akt途径抑制大鼠卵巢膜细胞的类固醇生成。因此，在H295R细胞中测试了白藜芦醇对PKB/Akt信号通路的影响，发现在饥饿生长条件下其作用减弱，但在正常生长条件下则不然。总体而言，这些作用特性以及最近的临床研究结果使白藜芦醇成为治疗如多囊卵巢综合征等高雄激素性疾病的候选药物。
