TY - JOUR T1 - The effect of tamoxifen on IGF signaling pathway in the mouse ovary AU - Asmaz, Ender Deniz AU - Zık, Berrin PY - 2019 DA - September DO - 10.33988/auvfd.498411 JF - Ankara Üniversitesi Veteriner Fakültesi Dergisi JO - Ankara Univ Vet Fak Derg PB - Ankara University WT - DergiPark SN - 1300-0861 SP - 343 EP - 350 VL - 66 IS - 4 LA - en AB - Tamoxifen (TAM) is one of selective estrogenreceptor modulators used in breast cancer treatment and prevention. The objective of this study wasto determine whether or not insulin-like growth factor-I (IGF-1) and itsreceptor (IGF-1R), has any role in the effect mechanism of TAM on the ovary.Experimentally, animals were divided into three groups as control group (n=20), low dose TAM treatment group (0.5 mg/mouse/day, n= 20) and high dose TAMtreatment group (1.5 mg/mouse/day, n= 20). TAM was injected 0.5 and 1.5mg/mouse/day for 5 days. Ovarian sections were used to examine the generalstructure by trichrome staining method and to determine IGF-1 and IGF-1Rexpressions by immunohistochemical staining method. After the experiment, thepresence of atretic follicles and small cystic structures in the TAM-treatedanimals was determined. Also, antral follicles and the corpus luteum were muchless in the high dose TAM group than in the control. TAM did not change theexpression of IGF-1 in granulosa cells, but increased the expression of IGF-1R.In TAM groups, IGF-1 and IGF-1R expression were increased in oocytes offollicles and in interstitial cells depending on TAM doses. However, whileIGF-1 expression was unchanged in the corpus luteum, decreased in treatmentgroup. TAM generally stimulated IGF-1 and IGF-1R expression in a dose-dependentmanner. The results suggest that IGF-1 signaling pathway is involved in themechanism of action of TAM on the ovary. We may assert that it may be useful touse IGF-1 signaling pathway regulators to adjust the effects of TAM on theovary. KW - : IGF-1 KW - IGF-1R KW - mouse KW - ovary KW - reproduction KW - tamoxifen CR - 1. Akduman AT, Özerkan K, Zik B, et al (2014): Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind trial in a mouse model. J Turk Ger Gynecol Assoc, 15, 228-232. CR - 2. Akkaya OO, Altunbas K, Yagcı A (2017): Effects of methoxychlor on IGF-1 signaling pathway in rat ovary. Biotech Histochem, 92, 230-242. CR - 3. Armstrong DG, Gutierrez CG, Baxter G, et al (2000): Expression of mRNA encoding IGF-1, IGF-1I and type 1 IGF receptor in bovine ovarian follicles. J Endocrinol, 165, 101-113. CR - 4. Armstrong DG, Webb R (1997): Ovarian follicular dominance: the role of intraovarian growth factors and novel proteins. Rev Reprod, 2, 139–146. CR - 5. Baumgarten SC, Convissar SM, Fierro MA, et al (2014): IGF1R signaling is necessary for FSH-induced activation of AKT and differentiation of human cumulus granulosa cells. J Clin Endocrinol Metab, 99, 2995-3004. CR - 6. Cara JF, Rosenfield RL (1988): Insulin-like growth factor I and ınsulin potentiate luteinizing hormone-ınduced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology, 123, 733-739. CR - 7. Cohen I, Figer A, Tepper R, et al (1999): Ovarian overstimulation and cystic formation in premenopausal tamoxifen exposure: comparison between tamoxifen treated and nontreated breast cancer patients. Gynecol Oncol, 72, 202-207. CR - 8. Crossman G (1937): A modification of Mallory’s connective tissue stain with a discussion of the principles involved. Anat Rec, 69, 33-38. CR - 9. Cruickshank J, Grossman DI, Peng RK, et al (2005): Spatial distribution of growth hormone receptor, insulin-like growth factor-I receptor and apoptotic chondrocytes during growth plate development. J Endocrinol, 184, 543-553. CR - 10. Ergin K, Gursoy E, Baġımoğlu-Koca Y, et al (2008): Immunohistochemical detection of insulin-like growth factor-I, transforming growth factor-b2, basic fibroblast growth factor and epidermal growth factor-receptor expression in developing rat ovary. Cytokine, 43, 209-214. CR - 11. Fu Z, Noguchi T, Kato H (2001): Vitamin a deficiency reduces insulin-like growth factor (IGF)-I gene expression and increases IGF-1 receptor and insulin receptor gene expression in tissues of japanese quail (coturnix coturnix japonica). J Nutr, 131, 1189-1194. CR - 12. Guthrie HD, Garrett WM, Cooper BS (1998): Follicle-stimulating hormone and insulin-like growth factor-I attenuate apoptosis in cultured porcine granulosa cells. Biol Reprod, 58, 390-396. CR - 13. Higgins MJ, Baselga J (2011): Targeted therapies for breast cancer. J Clin Invest, 121, 3797-3803. CR - 14. Hu CL, Cowan RG, Harman RM, et al (2004): Cell cycle progression and activation of akt kinase are required for insulin-like growth factor I-mediated suppression of apoptosis in granulosa cells. Mol Endocrinol, 18, 326-338. CR - 15. Kwintkiewicz J, Giudice LC (2009): The interplay of insulin-like growth factors, gonadotropins, and endocrine disruptors in ovarian follicular development and function. Semin Reprod Med, 27, 43-51. CR - 16. Luigi LD, Conti FG, Casini A (1997): Growth hormone and insulin-like growth factor I responses to moderate submaximal acute physical exercise in man: effects of octreotide, a somatostatin analogue, administration. Int J Sports Med, 18, 257-263. CR - 17. Macgregor JI, Jordan C (1998): Basic guide to the mechanisms of antiestrogens. Pharmacol Rev, 50, 151-196. CR - 18. Mahran YF, El-Demerdash E, Nada AS, et al (2013): Insights into the protective mechanisms of tamoxifen in radiotherapy-induced ovarian follicular loss: Impact on insulin-like growth factor 1. Endocrinology, 154, 3888-3899. CR - 19. Mazerbourg S, Bondy CA, Zhou J, et al (2003): The insulin-like growth factor system: a key determinant role in the growth and selection of ovarian follicles? a comparative species study. Reprod Domest Anim, 38, 247-258. CR - 20. Monget P, Fabre S, Mulsant P, et al (2002): Regulation of ovarian folliculogenesis by IGF and BMP system in domestic animals. Domest Anim Endocrinol, 23, 139-154. CR - 21. Monniaux D, Pisselet C (1992): Control of proliferation and differentiation of ovine granulosa cells by insulin-like growth factor-I and follicle-stimulating hormone in vitro. Biol Reprod, 46, 109-119. CR - 22. Mourits MJE, Vries EGE, Willemse PHB, et al (1999): Ovarian cysts in women receiving tamoxifen for breast cancer. Br J Cancer, 79, 1761-1764. CR - 23. O'Regan RM, Cisneros A, England GM, et al (1998): Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth. J Natl Cancer Inst, 90, 1552-1558. CR - 24. Pasqualini JR, Sumida C, Giambiagi N (1998): Pharmacodynamic and biological effects of anti-estrogens in different models. J Steroid Biochem, 31, 613-643. CR - 25. Perks CM, Peters AR, Wathes DC (1999): Follicular and luteal expression of insulin-like growth factors I and II and the type 1 IGF receptor in the bovine ovary. J Reprod Fertil, 116, 157-165. CR - 26. Pollak MN, Huynh HT, Lefebvre SP (1992): Tamoxifen reduces serum insulin-like growth factor I (IGF-1). Breast Cancer Res Treat, 22, 91-100. CR - 27. Qu J, Godin PA, Nisolle M, et al (2000): Expression of receptors for insulin-like growth factor-I and transforming growth factor-β in human follicles. Mol Hum Reprod, 6, 137-145. CR - 28. Quirk SM, Cowan RG, Harman RM, et al (2004): Ovarian follicular growth and atresia: the relationship between cell proliferation and survival. J Anim Sci, 82, 40-52. CR - 29. Ramachandran C, Khatib Z, Petkarou A, et al (2004): Tamoxifen modulation of etoposide cytotoxicity involves inhibition of protein kinase C activity and insulin-like growth factor II expression in brain tumor cells. J Neurooncol, 67, 19-28. CR - 30. Rzepczynska IJ, Piotrowski PC, Wong DH, et al (2009): Role of isoprenylation in Simvastatin-Induced inhibition of ovarian theca-interstitial growth in the rat. Biol Reprod, 81, 850-855. CR - 31. Sherman BM, Chapler FK, Crickard K, et al (1979): Endocrine consequences of continuous antiestrogen therapy with tamoxifen in premenopausal women. J Clin Invest, 64, 398-404. CR - 32. Shushan A, Peretz T, Uziely B, et al (1996): Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with breast cancer. Am J Obstet Gynecol, 174, 141-144. CR - 33. Spicer LJ, Chamberlain CS (1998): Influence of cortisol on insulin- and insulin-like growth factor 1 (IGF-1)-induced steroid production and on IGF-1 receptors in cultured bovine granulosa cells and thecal cells. Endocrine, 9, 153-161. CR - 34. Terada S, Uchide K, Suzuki N (1993): A follicular cyst during tamoksifen therapy in a premenopausal breast cancer woman. Gynecol Obstet Invest, 35, 62-64. CR - 35. Thissen JP, Ketelslegers JM, Underwood LE (1994): Nutritional regulation of the insulin-like growth factors. Endocr Rev, 15, 80-163. CR - 36. Ting AY, Kimler BF, Fabian CJ, et al (2008): Tamoxifen prevents premalignant changes of breast but not ovarian cancer in rats at high risk for both diseases. Cancer Prev Res, (Phila) 1, 546-553. CR - 37. Ting AY, Petroff BK (2010): Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat. J Assist Reprod Genet, 27, 591-597. CR - 38. Toda K, Miyaura C, Okada T, et al (2002): Dietary bisphenol a prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp19). Eur J Biochem, 269, 2214-2222. CR - 39. Tsujioka S, Ban Y, Wise LD, et al (2009): Collaborative work on evaluation of ovarian toxicity. 3) Effects of 2- or 4- week repeated dose toxicity and fertility studies with tamoksifen in female rats. J Toxicol Sci, 34, 43-51. CR - 40. Tucker MJ, Adam HK, Patterson JS (1984): Tamoxifen. 125-161. In: DR Laurence, AEM McLean, M Wetherall (Eds), Safety Testing of New Drugs, Laboratory Predictions and Clinical Performance. Academic. Press, London. CR - 41. Wandji SA, Wood TL, Crawford J, et al (1998): Expression of mouse ovarian insulin growth factor system components during follicular development and atresia. Endocrinology, 139, 5205-5214. CR - 42. Werner H, Shen-Orr Z, Stannard B, et al (1990): Experimental diabetes ıncreases ınsulinlike growth factor I and II receptor concentration and gene expression in kidney. Diabetes, 39, 1490-1497. CR - 43. Zhou J, Chin E, Bondy C (1991): Cellular pattern of insulin-like factor-I (IGF-1) and IGF-1 receptor gene expression in the developing and mature ovarian follicle. Endocrinology, 129, 3281-3288. CR - 44. Zhou P, Baumgarten SC, Wu Y, et al (2013): IGF-1 signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells. Mol Endocrinol, 27, 511-523. UR - https://doi.org/10.33988/auvfd.498411 L1 - https://dergipark.org.tr/en/download/article-file/803660 ER -