The Effect of Capsaicin on IGF-I and IGF-IR Expression in Ovarian Granulosa Cells


Keywords:
ovary capsaicin IGF-I IGF-IR
S. GULER
Β. ZIK
Abstract

Capsaicin (trans-8-methyl-N-vanillyl-6-noneadamide) is a pungent ingredient in red peppers from the Capsicum family. Insulin-like growth factor-I (IGF-I) is expressed in granulosa cells and has an important role in ovarian development. However, there are no data about the IGF-I expression in ovarian granulosa cells after capsaicin treatment. The aim of this study was to investigate the expression of IGF-I and its receptor (insulin-like growth factor-I receptor [IGF-IR]) in primary rat ovarian granulosa cells after low and high doses of capsaicin treatment. For this, granulosa cells were isolated and cultured from ovaries of 30-day-old female Sprague-Dawley rats. Granulosa cell plates were divided into four groups as cell control (C), vehicle control (V), and 50 μM and 150 μM capsaicin groups. In experimental groups, granulosa cells were exposed to capsaicin for 24 hours and immunocytochemistry was performed afterwards using anti-IGF-I and anti-IGF-IR antibodies. Both IGF-I and IGF-IR expressions were found to be significantly increased in parallel to the capsaicin doses. Elevated levels of IGF-I may be a risk factor for ovarian development. Because of the crucial role of IGF-I in ovary development, capsaicin treatment can be effective on follicular development and/or disorders characterized by high IGF-I levels.

Article Details
  • Section
  • Research Articles
Downloads
Download data is not yet available.
References
Adashi EY, Resnick CE, Svoboda ME, Van Wyk JJ (1985) Somatomedin-C synergizes with follicle-stimulating hormone in the acquisition of progestin biosynthetic capacity by cultured rat granulosa cells. Endocrinology 116:2135-2142.
Alatriste V, Herrera-Camacho I, Martinez MI, Limon ID, Gonzalez-Flores O, Luna F (2013) Sensory denervation with capsaicin reduces ovarian follicular development and delays the onset of puberty in guinea pigs. Advances in Reproductive Sciences 1(3):29-37.
Armstrong DG, Webb R (1997) Ovarian follicular dominance: the role of intraovarian growth factors and novel proteins. Rev Reprod 2:139-146.
Armstrong DT, Xia P, De Gannes G, Tekpetey FR, Khamsı F (1996) Differential effects of insulin-like growth factor-I and follicle-stimulating hormone on proliferation and differentiation of bovine cumulus cells and granulosa cells. Biol. Reprod 54:331-338.
Arora R, Gill NS, Chauhan G, Rana AC (2011) An overview about versatile molecule capsaicin. International Journal of Pharmaceutical Sciences and Drug Research 3(4):280-286.
Baker DM, Davıes B, Dıckhoff WW, Swanson P (2000) Insulin-like growth factor I increases follicle-stimulating hormone (FSH) content and gonadotropin-releasing hormone-stimulated FSH release from coho salmon pituitary cells in vitro. Biol Reprod 63(3):865-871.
Baserga R (1995) The insulin-like growth factor I receptor: a key to tumor growth?. Cancer Res 55(2): 249-252.
Baserga R (2000) The contradictions of the insulin-like growth factor 1 receptor. Oncogene 19(49): 5574-5581.
Baumgarten SC, Armouti M, Ko C, Stocco C (2017) IGF1R expression in ovarian granulosa cells is essential for steroidogenesis, follicle survival, and fertility in female mice. Endocrinology 158:2309-2318.
Campbell BK, Scaramuzzi RJ, Webb R (1995) Control of antral follicle development and selection in sheep and cattle. J Reprod Fertil Suppl 49:335-350.
Cansu A, Giray SG, Serdaroglu A, Erdogan D, Coskun KZ, Korucuoglu U, Biri AA (2008) Effects of chronic treatment with valproate and oxcarbazepine on ovarian folliculogenesis in rats. Epilepsia 49(7):1192-1201.
Chen HX, Sharon E (2013) IGF-1R as an anti-cancer target-trials and tribulations. Chin J Cancer 32(5): 242-252.
Caprodossi S, Amantini C, Nabissi M, Morelli MB, Farfariello V, Santoni M, Gismondi A, Santoni G (2011) Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells. Carcinogenesis 32 (5) : 686-694.
Daughaday WH, Rotwein P (1989) Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 10: 68-91.
Davoren JB, Hsueh AJW (1984) Insulin enhances FSH-stimulated steroidogenesis by cultured rat granulosa cells. Mol Cell Endocrinol 35(2-3): 97-105.
el-Roeiy A, Chen X, Roberts VJ, LeRoith D, Roberts CT Jr, Yen SS (1993) Expression of insulin-like growth factor-I (IGF-I) and IGF-II and the IGF-I, IGF-II, and insulin receptor genes and localization of the gene products in the human ovary. J Clin Endocrinol Metab 77 :1411-1418.
Guler S, Zık B (2018) Effects of capsaicin on ovarian granulosa cell proliferation and apoptosis. Cell and Tissue Research 372(3): 603-609.
Hernandez ER, Roberts CT, LeRoith D, Adashi EY (1989) Rat Ovarian Insulin-Like Growth Factor I (Igf-I) Gene Expression is Granulosa Cell-Selective: 5′-Untranslated mRNA Variant Representation and Hormonal Regulation. Endocrinology 125 (1) 572-574.
Holloway AC, Petrik JJ, Younglai EV (2007) Influence of dichlorodiphenylchloroethylene on vascular endothelial growth factor and insulin-like growth factor in human and rat ovarian cells. Reprod Toxicol 24(3-4): 359-364.
Jessell TM, Iversen LL, Cuello AC (1978) Capsaicin-induced depletion of substance P from primary sensory neurones. Brain Res 152:183-188.
Josse AR, Sheerffs SS, Holwerda AM, Andrews R, Staples AW, Philips SM (2010) Effects of capsinoid digestion on energy expenditure and lipid oxidation at rest and during exercise. Nutr Metab 7: 65.
Kadakia R, Arraztoa JA, Bondy C, Zhou J (2001) Granulosa cell proliferation is impaired in the Igf1 null ovary. Growth Horm IGF Res 11:220-224.
King SM, Modi DA, Eddie SL, Burdette JE (2013) Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway. J Ovarian Res 6(1): 12.
Li Y, Cai J, Han Y, Xiao X, Meng XL, Su L, Liu FY, Xing GG, Wan Y (2014) Enhanced function of TRPV1 via up-regulation by insulin-like growth factor-1 in a rat model of bone cancer pain. Eur J Pain 18(6):774-784.
Lilja J, Laulund F, Forsby A (2007) Insulin and insulin‐like growth factor type‐I up‐regulate the vanilloid receptor‐1 (TRPV1) in stably TRPV1‐expressing SH‐SY5Y neuroblastoma cells. Journal of Neuroscience Research 85(7): 1413-1439.
Maestro MA, Planas JV, Moriyama S, Gutiérrez J, Planas J, Swanson P (1997) Ovarian receptors for insulin and insulin-like growth factor I (IGF-I) and effects of IGF-I on steroid production by isolated follicular layers of the preovulatory coho salmon ovarian follicle. Gen Comp Endocrinol 106(2): 189-201.
Morán C, Morales L, Razo RS, Apolonio J, Quiróz U, Chavira R, Domínguez R (2003) Effects of sensorial denervation induced by capsaicin injection at birth or on day three of life, on puberty, induced ovulation and pregnancy. Life Sci 73(16): 2113-2125.
Nagy I, Santha P, Jancso G, Urban L (2004) The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology. Eur J Pharmacol 500: 351-369.
Nakagawa H, Hiura A (2006) Capsaicin, transient receptor potential (TRP) protein subfamilies and the particular relationship between capsaicin receptors and small primary sensory neurons. Anat Sci Int 81: 135-155.
Ozden-Akkaya O, Altunbas K, Yagcı A (2017) Effects of methoxychlor on IGF-I signaling pathway in rat ovary. Biotech Histochem 92(3):230-242.
Ozer A, Erdost H, Zik B (2005) Histological investigations on the effects of feeding a diet containing red hot pepper on the reproductive organs of the chicken. Phytother Res 19: 501-505.
Pintado CO, Pinto FM, Pennefather JN, Hidalgo A, Baamonde A, Sanchez T, Candenas ML (2003) A role tachykinins in female mouse and rat reproductive function. Biol Reprod 69: 219-226.
Saria A, Ma RC, Dun NJ, Theodorsson-Norheim E, Lundberg JM (1987) Neurokinin A in capsaicin-sensitive neuronsof the guinea-pig inferior mesenteric ganglia: an additional putative mediator for the non-cholinergic excitatory postsynaptic potential. Neuroscience 21: 951-958.
Schildkraut JM, Schwingl PJ, Bastos E, Evanoff A, Hughes C (1996) Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol 88: 554-559.
Sharma SK, Vij AS, Sharma M (2013) Mechanisms and clinical uses of capsaicin. Eur J Pharmacol 720(1-3): 55-62.
Sirotkin AV (2011) Growth factors controlling ovarian functions. J Cell Physiol 226(9): 2222-2225.
Surh YJ, Lee SS (1996) Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol 34: 313-316.
Stubbs SA, Webber LJ, Stark J, Rice S, Margara R, Lavery S, Trew GH, Hardy K, Franks S (2013) Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries. J Clin Endocrinol Metab 98(8): 3298-3305.
Traurig H, Saria A, Lembeck F (1984) The effects of neonatal capsaicin treatment on growth and subsequent reproductive function in the rat. Naunyn-Schmiedeberg’s Arch Pharmacol 327(3): 254-259.
Uzumcu M, Lin YC (1994) Characterization of the stimulatory actions of thymic factor(s) on basal and gonadotropin-induced steroidogenesis in cultured rat granulosa cells. Mol Cell Endocrinol 105: 209-216.
Van Buren JJ, Bhat S, Rotello R, Pauza ME, Premkumar LS (2005) Sensitization and translocation of TRPV1 by insulin and IGF‐I. Mol Pain 1: 17.
Wardle KA, Ranson J, Sanger GJ (1997) Pharmacological characterization of the vallinoid receptor in the rat dorsal spinal cord. British Journal of Pharmacology 121:1012-1016.
Wood AM, Lambert A, Higham V (1993) Insulin-like growth factor-I stimulated growth and progesterone production by granulosa-lutein cells. Lack of interaction with physiological concentrations of luteinizing hormone and follicle stimulating hormone. Hum Reprod 8:1813-1818.
Xia P, Tekpetey FR, Armstrong DT (1994) Effect of IGF-I on pig oocyte maturation, fertilization, and early embryonic development in vitro, and on granulosa and cumulus cell biosynthetic activity. Mol Reprod Dev 38: 373-379.
Zachow R, Uzumcu M (2006) The methoxychlor metabolite, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits steroidogenesis in rat ovarian granulosa cells in vitro. Reproductive Toxicology 22(4):659-665.
Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK (2008) In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13(12): 1465-1478.
Zhou P, Baumgarten SC, Wu Y, Bennett J, Winston N, Hirshfeld-Cytron J, Stocco C (2013) IGF-I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells. Mol. Endocrinol 27(3): 511-523.
Zik B, Ozguden Akkoc CG, Tutuncu S, Tuncay I, Yilmaztepe OA, Ozenci CC (2010) Effect of low dose capsaicin (CAP) on ovarian follicle development in prepubertal rat. Revue Med Vet 161: 288-294.