RRC ID 43684
著者 Morita Y, Wada-Hiraike O, Yano T, Shirane A, Hirano M, Hiraike H, Koyama S, Oishi H, Yoshino O, Miyamoto Y, Sone K, Oda K, Nakagawa S, Tsutsui K, Taketani Y.
タイトル Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary.
ジャーナル Reprod Biol Endocrinol
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.
巻・号 10
ページ 14
公開日 2012-2-23
DOI 10.1186/1477-7827-10-14
PII 1477-7827-10-14
PMID 22357324
PMC PMC3311078
MeSH Adult Animals Apoptosis / drug effects Female Granulosa Cells / drug effects Granulosa Cells / metabolism* HeLa Cells Humans Middle Aged Phosphoproteins / biosynthesis Rats Rats, Wistar Resveratrol Sirtuin 1 / biosynthesis* Sirtuin 1 / physiology* Stilbenes / pharmacology*
IF 3.235
引用数 59
WOS 分野 REPRODUCTIVE BIOLOGY ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 KGN(RCB1154)