Document Type : Original Article
Authors
1 Department of Gamete and Cloning, Research Institute of Animal Embryo Technology, Shahrekord University, Shahrekord, Iran
2 Department of Biology, Faculty of Science, Shahrekord University, Shahrekord, Iran
Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors of transcription factors composed of three family members: PPARα, PPARβ/δ and PPARγ. This study was aimed to evaluate the role of PPARs in the estradiol production via follicle stimulating hormone (FSH) in the ovine Sertoli cells. At the first step, transcripts of PPARα, PPARβ /δ and PPARγ were evaluated by quantitative real time PCR (qRT-PCR) in the ovine Sertoli cells in vitro after FSH treatment. PPARγ transcript was increased in FSH-treated cells while PPARα and PPAR β /δ transcripts were unchanged. At the second step, Pioglitazone as PPARγ agonist and 2-chloro-5-nitrobenzanilide (GW9662) as PPARγ antagonist were used in the FSH-treated Sertoli cells and then, the estradiol production and aromatase transcript were evaluated. Aromatase transcript was increased by pioglitazone in the FSH-treated Sertoli cells while GW9662 did not change its transcript. The estradiol production was increased by low concentrations of pioglitazone in FSH-treated Sertoli cells while the production of this hormone was decreased by the high concentration of Pioglitazone. The GW9662 did not change the production of estradiol in FSH-treated Sertoli cells. It is concluded that FSH regulates the estradiol production and aromatase expression in a way independently of PPARβ/δ and PPARα activation, although FSH increases the transcript of PPARγ and in this way, it could affect (mostly increase) aromatase transcript and estradiol production. Probably, this effect of FSH in the estradiol production via PPARγ is only a servo-assist mechanism which if it was inhibited, the estradiol production was not considerably affected.
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- Sorensen H, Treuter E, Gustafsson J. Regulation of peroxisome proliferator-activated receptors. Vitam Horm 1998; 54: 121-166.
- Froment P, Gizard F, Defever D, et al. Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition. J Endocrinol 2006; 189: 199-209.
- Douard V, Hermier D, Magistrini M, et al. Reproductive period affects lipid composition and quality of fresh and stored spermatozoa in turkeys. Theriogenology 2003; 59: 753-764.
- Staels B, Fruchart J. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005; 54: 2460-2470.
- Debril M, Renaud J, Fajas L, et al. The pleiotropic functions of peroxisome proliferator-activated receptor gamma. J Mol Med 2001; 79: 30-47.
- Hara S, Takahashi T, Amita M, et al. Pioglitazone counteracts the tumor necrosis factor-α inhibition of follicle-stimulating hormone-induced follicular development and estradiol production in an in vitro mouse preantral follicle culture system. J Ovarian Res 2013; 6: 1-8.
- Bhattacharya N, Dufour JM, Vo MN, et al. Differential effects of phthalates on the testis and the liver. Biol Reprod 2005; 72: 745-754.
- Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha,-beta, and-gamma in the adult rat. Endocrinology 1996; 137: 354-366.
- Kadivar A, Heidari Khoei H, Hassanpour H, et al. Peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARβ/δ) gene expression profile on ram spermatozoa and their relation to the sperm motility. Vet Res Forum 2016; 7: 27-34.
- Walker WH, Cheng J. FSH and testosterone signaling in Sertoli cells. Reproduction 2005; 130: 15-28.
- Skinner MK. Sertoli cell secreted regulatory factors Sertoli cell biology. San Diego, USA: Elsevier Science 2005:107-120.
- Izadyar F, Spierenberg G, Creemers L. Isolation and purification of type A spermatogonia from the bovine testis. Reproduction 2002; 124: 85-94.
- Hassanpour H, Kadivar A, Mirshokraei P, et al. Connexin-43: A possible mediator of heat stress effects on ram Sertoli cells. Vet Res Forum 2015; 6: 125-130.
- Minaee Zanganeh B, Roudkenar M, Kashani IR. Co-culture of spermatogonial stem cells with Sertoli cells in the presence of testosterone and fsh improved differentiation via up-regulation of post meiotic genes. Act Med Iranica 2013; 51: 1-11.
- Hassanpour H, Mirshokraei P, Khalili Sadrabad E, et al. In vitro effect of nanosilver on gene expression of superoxide dismutases and nitric oxide synthases in chicken Sertoli cells. Animal 2015; 9: 295-300.
- Ahmadipour B, Hassanpour H, Asadi E, et al. Kelussia odoratissima Mozzaf- A promising medicinal herb to prevent pulmonary hypertension in broiler chickens reared at high altitude. J Ethnopharmacol 2015; 159: 49-54.
- Hassanpour H, Afzali A, Bahadoran S. Diminished gene expression of cardiac heat shock proteins in pulmonary hypertensive chickens. Br Poult Sci 2013; 54: 581-586.
- Primers-BLAST: A tool for finding specific primers. Available at: https://www.ncbi.nlm.nih.gov/tools/primer-blast/index.cgi?LINK_LOC=BlastHome. Accessed at Oct 12, 2014.
- Standard Nucleotide BLAST. Available at: https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE_TYPE=BlastSearch.Accessed at October 12, 2014.
- Ruijter JM, Ramakers C, Hoogaars WMH, et al. Amplification efficiency: Linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res 2009; 7:e45. doi:10.1093/nar/gkp045.
- Dorak M. Real Time PCR. Oxford, UK: Taylor & Francis 2006: 41-62.
- Hassanpour H, Nikoukara Z, Nasiri L, et al. Differential gene expression of three nitric oxide synthases is consistent with increased nitric oxide in the hindbrain of broilers with cold-induced pulmonary hypertension. Br Poult Sci 2015; 56: 436-442.
- McDonald CA, Millena AC, Reddy S, et al. Follicle-stimulating hormone-induced aromatase in immature rat Sertoli cells requires an active phosphatidylinositol 3-kinase pathway and is inhibited via the mitogen-activated protein kinase signaling pathway. Mol Endocrinol 2005; 20: 608-618.
- Matzkin M, Pellizzari E, Rossi S, et al. Exploring the cyclooxygenase 2 (COX2)/15d-Δ -12, 14 PGJ 2 system in hamster Sertoli cells: Regulation by FSH/ testosterone and relevance to glucose uptake. Gen Comp Endocrinol 2012; 179: 254-264.
- Grygiel-Gorniak B. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications- a review. Nutr J 2014; 13: 1-10.
- Froment P, Fabre Sp, Dupont Jl, et al. Expression and functional role of peroxisome proliferator-activated receptor-γ in ovarian folliculogenesis in the sheep. Biol Reprod 2003; 69: 1665-1674.
- Schultz Rd, Yan W, Toppari J, et al. Expression of peroxisome proliferator-activated receptor γ messenger ribonucleic acid and protein in human and rat testis. Endocrinology 1999; 140: 2968-2975.
- Mu YM, Yanase T, Nishi Y, et al. Insulin sensitizer, troglitazone, directly inhibits aromatase activity in human ovarian granulosa cells. Biochem Biophys Res Commun 2000; 271: 710-713.
- Schoppee PD, Garmey JC, Veldhuis JD. Putative activation of the peroxisome proliferator-activated receptor gamma impairs androgen and enhances progesterone biosynthesis in primary cultures of porcine theca cells. Biol Reprod 2002; 66: 190-198.
- Lohrke B, Viergutz T, Shahi SK, et al. Detection and functional characterisation of the transcription factor peroxisome proliferator-activated receptor gamma in lutein cells. J Endocrinol 1998; 159: 429-439.
- Komar CM, Braissant O, Wahli W, et al. Expression and localization of PPARs in the rat ovary during follicular development and the periovulatory period. Endocrinology 2001; 142: 4831-4838.
- Subbaramaiah K, Howe LR, Zhou XK, et al. Pioglitazone, a PPARγ agonist, suppresses CYP19 transcription: evidence for involvement of 15-hydroxyprostaglandin dehydrogenase and BRCA1. Cancer Prev Res 2012; 5: 1183-1194.
- Kwintkiewicz J, Giudice LC. Endocrine disruptor bisphenol A induces expression of peroxisome proliferator-activated receptor γ which contributes to down-regulation of FSH-stimulated aromatase expression and estradiol production in human granulosa KGN cells. Biol Reprod 2008; 78: 199.
- Redondo S, Ruiz E, Santos-Gallego CG, et al. Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-gamma, transforming growth factor-beta, and a Smad2-dependent mechanism. Diabetes 2005; 54: 811-817.
- Sharma I, Singh D. Conjugated linoleic acids attenuate FSH-and IGF1-stimulated cell proliferation; IGF1, GATA4, and aromatase expression; and estradiol-17β production in buffalo granulosa cells involving PPARγ, PTEN, and PI3K/Akt. Reproduction 2012; 144: 373-383.
- Seargent JM, Yates EA, Gill JH. GW9662, a potent antagonist of PPARγ, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARγ agonist rosiglitazone, independently of PPARγ activation. Br J Pharmacol 2004; 143: 933-937.
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