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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2012

Open Access 01-12-2012 | Research

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

Authors: Yoshihiro Morita, Osamu Wada-Hiraike, Tetsu Yano, Akira Shirane, Mana Hirano, Haruko Hiraike, Satoshi Koyama, Hajime Oishi, Osamu Yoshino, Yuichiro Miyamoto, Kenbun Sone, Katsutoshi Oda, Shunsuke Nakagawa, Kazuyoshi Tsutsui, Yuji Taketani

Published in: Reproductive Biology and Endocrinology | Issue 1/2012

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Abstract

Background

Resveratrol 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.

Methods

The 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.

Results

SIRT1 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.

Conclusions

These 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.
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Metadata
Title
Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary
Authors
Yoshihiro Morita
Osamu Wada-Hiraike
Tetsu Yano
Akira Shirane
Mana Hirano
Haruko Hiraike
Satoshi Koyama
Hajime Oishi
Osamu Yoshino
Yuichiro Miyamoto
Kenbun Sone
Katsutoshi Oda
Shunsuke Nakagawa
Kazuyoshi Tsutsui
Yuji Taketani
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2012
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-10-14

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