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

Reproductive Biology and Endocrinology

Yuji Taketani²  Kazuyoshi Tsutsui³  Shunsuke Nakagawa¹  Katsutoshi Oda²  Kenbun Sone²  Yuichiro Miyamoto²  Osamu Yoshino²  Hajime Oishi²  Satoshi Koyama²  Haruko Hiraike²  Mana Hirano²  Akira Shirane²  Tetsu Yano²  Osamu Wada-Hiraike²  Yoshihiro Morita² 

[1] Department of Obstetrics and Gynecology, School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan;Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, 2-2, Wakamatsuchou, Shinjuku-ku, Tokyo, 162-8480, Japan

关键词: Luteinization;    Granulosa cells;    Ovary;    Resveratrol;    SIRT1;   

Others  :  1151023
DOI  :  10.1186/1477-7827-10-14

 received in 2011-09-05, accepted in 2012-02-23,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Morita et al; licensee BioMed Central Ltd.

【 图 表 】

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