The online version of this article (doi:10.1186/1477-7827-10-14) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
YM carried out all of the experiments. AS, MH, HH, YM, and KS participated in the immunohistochemistry, real time PCR, Western blot, and hormonal quantification. OY helped to collect and purify rat GCs. SK, MH, and HO helped to collect human luteinized GCs from follicular aspirates. OW-H has been involved in acquisition of data, drafting the manuscript, and revising it critically for important intellectual content. KO, SN, and TY have made substantial contributions to conception and design, analysis and interpretation of data. KT and YT have given final approval of the version to be submitted. All authors read and approved the final manuscript.
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.
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.
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.
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.
Joe AK, Liu H, Suzui M, Vural ME, Xiao D, Weinstein IB: Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res. 2002, 8 (3): 893-903. PubMed
van Ginkel PR, Sareen D, Subramanian L, Walker Q, Darjatmoko SR, Lindstrom MJ, Kulkarni A, Albert DM, Polans AS: Resveratrol inhibits tumor growth of human neuroblastoma and mediates apoptosis by directly targeting mitochondria. Clin Cancer Res. 2007, 13 (17): 5162-5169. 10.1158/1078-0432.CCR-07-0347. CrossRefPubMed
Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M, Nomura M, Mukasa C, Okabe T, Goto K, et al: Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology. 2001, 142 (1): 437-445. 10.1210/en.142.1.437. CrossRefPubMed
Chen Q, Yano T, Matsumi H, Osuga Y, Yano N, Xu J, Wada O, Koga K, Fujiwara T, Kugu K, et al: Cross-Talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulosa cell apoptosis: a possible regulatory mechanism for ovarian follicle atresia. Endocrinology. 2005, 146 (2): 808-815. CrossRefPubMed
Wada-Hiraike O, Hiraike H, Okinaga H, Imamov O, Barros RP, Morani A, Omoto Y, Warner M, Gustafsson JA: Role of estrogen receptor beta in uterine stroma and epithelium: Insights from estrogen receptor beta-/-mice. Proc Natl Acad Sci USA. 2006, 103 (48): 18350-18355. 10.1073/pnas.0608861103. PubMedCentralCrossRefPubMed
Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM: Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology. 2000, 141 (10): 3657-3667. 10.1210/en.141.10.3657. PubMed
Singh UP, Singh NP, Singh B, Hofseth LJ, Price RL, Nagarkatti M, Nagarkatti PS: Resveratrol (trans-3,5,4'-trihydroxystilbene) induces silent mating type information regulation-1 and down-regulates nuclear transcription factor-kappaB activation to abrogate dextran sulfate sodium-induced colitis. J Pharmacol Exp Ther. 2010, 332 (3): 829-839. 10.1124/jpet.109.160838. PubMedCentralCrossRefPubMed
Kiriakidou M, McAllister JM, Sugawara T, Strauss JF: Expression of steroidogenic acute regulatory protein (StAR) in the human ovary. J Clin Endocrinol Metab. 1996, 81 (11): 4122-4128. 10.1210/jc.81.11.4122. PubMed
- Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary
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