Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary

Abstract

BackgroundResveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary.MethodsThe physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining.ResultsSIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol.ConclusionsThese results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency.

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

“…However, it has been reported that resveratrol inhibits aromatase production in cultures of rat granulosa cells in vitro (53) and thus reduces the estrogen synthesis that leads to impaired folliculogenesis. In this context, it has been suggested that SIRT1 activation by resveratrol results in a significant increase of LH receptors in granulosa cells (62), and this polyphenol shows higher affinity for estrogen receptor (ER)-b (63) than for ER-a. Because LH is the main hormone responsible for ovulation, and actions mediated via interaction with ER-b may enhance ovulatory response (64), an alternative hypothesis for our results is that resveratrol could improve the ovulation rate through these receptors.…”

Expression and effect of NAMPT (visfatin) on progesterone secretion in hen granulosa cells

“…NAMPT is the rate-limiting enzyme in NAD biosynthesis, and it plays a critical role in several mammalian physiological processes (Revollo et al 2004, Imai 2009). In mammals, NAMPT regulates the activity of the sirtuin 1 (SIRT1) histone deacetylase (Revollo et al 2004), and it has been shown to be involved in the regulation of steroidogenesis (Morita et al 2012, Wu et al 2012. Sirtuins have not yet been identified in hen ovaries, but they may play a role in the effects of NAMPT on hen granulosa cell steroidogenesis.…”

Roles of SIRT1 in granulosa cell apoptosis during the process of follicular atresia in porcine ovary

“…It has been reported that SIRT1 protein was expressed in mouse ovarian tissues (Morita et al, 2012), human luteinized granulosa cells (Benayoun et al, 2011) and bovine oocytes (Ghinis-Hozumi et al, 2011). The present study showed that SIRT1 protein was widely expressed in porcine ovary.…”

“…SIRT1 can reduce ovarian cell viability, promote ovarian progesterone (P 4 ) release and expression of luteinization-related genes in the ovary of rodents (Morita et al, 2012). Meanwhile, transfection of cells with SIRT1 gene increased the accumulation of proliferation markers (Cdc2/p34, cyclin B1), decreased accumulation of p50 and p65, and stimulated release of IGF-I in porcine ovary (Pavlová et al, 2013).…”