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

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

    Research output: Contribution to journalArticle

    48 Citations (Scopus)

    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.

    Original languageEnglish
    Article number14
    JournalReproductive Biology and Endocrinology
    Volume10
    DOIs
    Publication statusPublished - 2012 Feb 23

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    Sirtuin 1
    Granulosa Cells
    Ovary
    Cell Survival
    Messenger RNA
    Progesterone
    Homeostasis
    Western Blotting
    Sirtuins
    Luteinization
    FSH Receptors
    Apoptosis
    Caspase 7
    resveratrol
    LH Receptors
    Proteins
    Diethylstilbestrol
    Histone Deacetylases
    Aromatase
    Luteal Phase

    Keywords

    • Granulosa cells
    • Luteinization
    • Ovary
    • Resveratrol
    • SIRT1

    ASJC Scopus subject areas

    • Developmental Biology
    • Endocrinology
    • Reproductive Medicine
    • Medicine(all)

    Cite this

    Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells : An implicative role of SIRT1 in the ovary. / Morita, Yoshihiro; Wada-Hiraike, Osamu; Yano, Tetsu; Shirane, Akira; Hirano, Mana; Hiraike, Haruko; Koyama, Satoshi; Oishi, Hajime; Yoshino, Osamu; Miyamoto, Yuichiro; Sone, Kenbun; Oda, Katsutoshi; Nakagawa, Shunsuke; Tsutsui, Kazuyoshi; Taketani, Yuji.

    In: Reproductive Biology and Endocrinology, Vol. 10, 14, 23.02.2012.

    Research output: Contribution to journalArticle

    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 2012, 'Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: An implicative role of SIRT1 in the ovary', Reproductive Biology and Endocrinology, vol. 10, 14. https://doi.org/10.1186/1477-7827-10-14
    Morita, Yoshihiro ; Wada-Hiraike, Osamu ; Yano, Tetsu ; Shirane, Akira ; Hirano, Mana ; Hiraike, Haruko ; Koyama, Satoshi ; Oishi, Hajime ; Yoshino, Osamu ; Miyamoto, Yuichiro ; Sone, Kenbun ; Oda, Katsutoshi ; Nakagawa, Shunsuke ; Tsutsui, Kazuyoshi ; Taketani, Yuji. / Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells : An implicative role of SIRT1 in the ovary. In: Reproductive Biology and Endocrinology. 2012 ; Vol. 10.
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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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    author = "Yoshihiro Morita and Osamu Wada-Hiraike and Tetsu Yano and Akira Shirane and Mana Hirano and Haruko Hiraike and Satoshi Koyama and Hajime Oishi and Osamu Yoshino and Yuichiro Miyamoto and Kenbun Sone and Katsutoshi Oda and Shunsuke Nakagawa and Kazuyoshi Tsutsui and Yuji Taketani",
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    T1 - Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells

    T2 - An implicative role of SIRT1 in the ovary

    AU - Morita, Yoshihiro

    AU - Wada-Hiraike, Osamu

    AU - Yano, Tetsu

    AU - Shirane, Akira

    AU - Hirano, Mana

    AU - Hiraike, Haruko

    AU - Koyama, Satoshi

    AU - Oishi, Hajime

    AU - Yoshino, Osamu

    AU - Miyamoto, Yuichiro

    AU - Sone, Kenbun

    AU - Oda, Katsutoshi

    AU - Nakagawa, Shunsuke

    AU - Tsutsui, Kazuyoshi

    AU - Taketani, Yuji

    PY - 2012/2/23

    Y1 - 2012/2/23

    N2 - 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.

    AB - 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.

    KW - Granulosa cells

    KW - Luteinization

    KW - Ovary

    KW - Resveratrol

    KW - SIRT1

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