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Comparative Effects of Ovariectomy and Flutamid on Body-Uterus Weight and Uterine Histology in the Ovariectomized Rat Model+

Year 2006, Volume: 13 Issue: 4, 221 - 226, 01.08.2006

Abstract

Objective: To determine the effect of flutamide on uterine histology and to ascertain whether flutamide regulates body weight gain in the ovariectomized rat model. Materials and Methods: We used 36 sexually mature female Wistar-Albino rats in this study. The study was performed in the Department of Medical Science Application and Research Centre of Dicle University, Diyarbakir. We divided the model rats into 3 groups: group 1- control group, group 2- sham-operated group and group 3- bilaterally ovariectomized group. In addition, we gave flutamide to group 3. Results: We found that the body weight was higher in the ovariectomized rats than the control rats, unlike the decreased uterine net weight. Furthermore, body weight decreased slightly after flutamide therapy, however uterine net weight increased. After flutamide applications, the length of uterinal epithelium, the number of uterinal glands, infiltration of the stromal cells increased and the lumen of uterinal glands were dilateded. Conclusion: As a result, an improvement was observed after flutamide applications while bilateral ovariectomy was determined to cause atrophy in the uterine epithelium of rat. Our study may be source for further research examining the relationship between the androgen receptor antagonist flutamide and reproductive function in female rats. Key words: Flutamide, Anti-androgen, Ovariectomy, Uterine histology, Body weight

References

  • Smith EP, Boyd J, Frank GR, Takahashi H. Estrogen resistance caused by a mutation in the estrogen receptor gene in a man. N Engl J Med 1994; 331:1088-89.
  • Pelletier G, Labrie C, Labrie F. Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 2000; 165: 359-70.
  • Weihua Z, Saji S, Makinen S, Cheng G. Estrogen receptor beta, a modulator of ER alpha in the uterus. Proc Natl Acad 2000; 97: 5936-41.
  • Barrett Connor R, Young R, Notelovitz M, Sullivan J. A two-year double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. J Reprod Med 1999; 44:1012-20.
  • Beri R, Kumar N, Savage T, Benalcazar L, Sundaram K. Estrogenic and progestational activity of 7α-methyl-19-nortestosterone,a synthetic androgen. J Steroid Biochem Mol Biol 1998; 67: 275-83.
  • Sahlin L, Norstedt G, Eriksson H.Androgen regulation of the insulin- like growth factor,and the estrogen receptor in rat uterus and liver.J Steroid Biochem Mol Biol 1994; 51: 57-66.
  • Giannopoulos G.Binding of testosterone to cytoplasmic components of the immature rat uterus.Biochem Biophys Res Commun 1971; 44: 943-51.
  • Sahlin L, Wang H, Masironi B,Holmgren A, Eriksson H.Regulation of thioredoxin mRNA in the rat uterus by gonadal steroids. J Steroid Biochem Mol Biol 1999; 68: 203-09.
  • Jones RC, Edgren RA. The effects of various steroids on the vaginal histology in the rat. Fertil Steril 1973; 24: 284-91.
  • Okazaki K, Imazawa T, Nakamura H, Furukawa F, Nishikawa A. A repeated 28 day oral dose toxicity study of 17α-methyltestosterone in rats, based on the 'Enhanced OELD Test Guideline 407' for screening the endocrine- disrupting chemicals.Arch Toxical 2002; 75: 635-42.
  • Espuna G, Chuzel F, Esch GP, Pallen C, Bars R. Detection of endocrine effects, an enhaced OECD Test Guideline 407, Study with methyltestosterone.Toxical Sci 2002; 66:276.
  • Neumann F, Graf KJ, Hasan SH. Central actions of antiandrogens. In: L Martini and M Motta (eds). Androgens and antiandrogens, Raven press, Newyork. 1977; 163-77.
  • Neri R.O. Studies on the biology and mechanism of action of nonsteroidal antiandrogens. In: L Martini and M Motta (eds). Androgens and antiandrogens, Raven press, Newyork. 1977; 179-88.
  • Dukes M, Furr JA, Hughes LR. Nonsteroidal progestins and antiprogestins related to flutamide. Steroids 2000; 65: 725-31.
  • Pazo S.F., Sanchez F.F., Balsa J.A. Mechanisms of reduced body growth in the pubertal feminized male rat. Pediatr Res 2000; 48: 96-103.
  • Nguyen P.G., Duman H.J., Siliart B.S. Effects of dietary fat and energy on body weight and composition after gonadectomy in cats. Am J Vet Res 2004; 65: 1708-13.
  • Gray LE., Ostby JS. Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. Toxicol Appl Pharmacol 1994; 129:46-52.
  • Haskell CM. Cancer treatment, 3 rd ed. Philadelphia: WB Saunders Co. 1990; 96.
  • Jellinck PH., Newcombe A.M. Androgen receptor-mediated inhibition of oestrogen- ınduced uterine peroxidase. J Steroid Biochem 1983; 19:1713-17.
  • Karnam RP. Pao LW. Calogero D. Effects of surgıcal ovariectomy on rat salivary gland function. Archs oral Biol 1993; 38: 779-84.
  • Neter J, Wasserman W, Ahitmore GA. Applied Statistics. Boston: Allyn and Bacon 1982; 544- 72.
  • Taguchi O, Cunha GR, Robboy SJ. Experimental study of the effect of diethylstilbestrol on the development of the human female reproductive tract. Biol Res Pregnancy 1983; 4: 56
  • Fisher B, Redmond B, Brown A. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol 1986; 4: 459.
  • Dukes M, Furr JA, Hughes LR. Nonsteroidal progestins and antiprogestins related to flutamide. Steroids 2000;65 :725-31.
  • Schmidt WN, Katzenellen BS. Androgen-uterine interactions: an assessment of androgen interaction with the testosterone and estrogen receptor systems and stimulation of uterine growth and progesterone receptor synthesis. Moll Cell Endocrinol 1979; 15: 91-108.
  • Chandrasekhar Y, Armstrong DT. Regulation of uterine progesterone receptors by the nonsteroidal antiandrogen hydroxyflutamide. Biol Reprod 1991; 45: 78-81.
  • Basson R. Female sexual response the role of drugs in the management of sexual dysfunction. Obstet Gynecol 2001; 98:350-53.
  • Reznikov AG, Sinitsyn PV, Tarasenko LV. Neuroendocrine mechanisms of development of experimental hyperandrogen induced anovulation. Neurosci Behav Physiol 2003; 33: 773-6.
  • Kaori M, Setsuko Y, Masashi S. Effects of perinatal exposure to flutamide on sex hormone responsiveness in F1 male rats. The Journal of Toxicological Sciences 2003; 3:149-63.
  • Branham SW, Sheehan DM, Zehr DR. Inhibition of rat uterine gland genesis by tamoxifen. Endocrinol 1985; 117: 2238.
  • Branham SW, Sheehan DM, Zehr DR. The postnatal ontogeny of rat uterine glands and age related effects of 17 β estradiol. Endocrinol 1985; 117: 2229.
  • Kent J. Development of the infantile mouse uterus: the effect of stilbestrol. J Reprod Fertil 1975; 43:367
  • Clark JH, Mc Cormack SA, Kling R. Effect of clomiphene and other triphenylethylene derivatives on the reproductive tract in the rat and baboon. In: Lacobelli S. Hormones and Cancer 1980; 295.
  • Park SM, Park CH, Wha JD. Ahigh carbohydrate diet induces insulin resistance through decreased glucose utilization in ovariectomized rats. Korean J Intern Med 2004; 19: 87-92.
  • Blaustein JD, Gentry RT, Roy EJ. Effects of ovariectomy and estradiol on body weght and food intake in gold thioglucose treated mice. Physiol Behav 1976; 17: 1027-30.
  • Retra RN, Wenndy NJ, Joseph H. Developmental exposure to DES alters uterine response to estrogens in prepubescent mice: low versus high dose effects. Reprod Toxicol 2004; 18: 399-06.
  • Sutherland MK, Brady H, Gayo LM. Effects of SP 500263, a novel selective estrogen receptor modulator on bone, uterus and serum cholesterol in the ovariectomized rat. Calcif Tissue Int 2003; 72: 710-16.
  • Saruhan BG., Nergiz Y. Histological Effect of Estrogens and Anti-estrogens on uterinal epithelium in estrogen deficiency induced rats. Journal of Dicle Medicine 2002; 29: 1-2.
  • Saruhan BG., Nergiz Y. Histological Effect of Estrogens and Anti-estrogens on vaginal epithelium in estrogen deficiency induced rats. The Chamber of Medicine of Istanbul, Journal of Clinical Development 2003; 16: 1-5.
  • Corresponding Author
  • Dr. BernaGüney SARUHAN
  • Departments of Histology and Embryology,
  • Veterinary Medicine Faculty, University of Dicle, Diyarbakir
  • Tel : +90 412 248 8020-8627
  • Tel : +90 537-798 8616
  • E-Mail : bsaruhan@dicle.edu.tr

Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması

Year 2006, Volume: 13 Issue: 4, 221 - 226, 01.08.2006

Abstract

Amaç: Ovarektomize ratlarda Flutamid kullanımının vücut ağırlığı ve uterus dokusu üzerine etkilerinin araştırılması. Materyal ve Metod: 36 adet Wistar Albino türü dişi sıçanlar Dicle üniversitesi DÜSAM merkezinden seçildi. Sıçanlar 3 guruba ayrıldı. Grup 1 - kontrol grubu, grup 2 - sham-operasyon, grup 3-bilateral ovarektomi ve flutamid verilen grup. Bulgular: Çalışmada ovarektomize ratların vücut ağırlığı kontrol ratlardan daha fazla bulunurken, uterus ağırlığının azaldığı gözlemlenmiştir. Bununla birlikte flutamid kullanımı sonrasında vücut ağırlığı çok önemli olmamakla beraber azalırken uterus ağırlığı artmıştır. Flutamid uygulamasından sonra uterus epitelinin yüksekliği, uterinal bezlerin sayısı artarken bezlerin lumenlerinde genişleme gözlemlenmiştir. Sonuç: Bilateral ovarektomi ratların uterus epitelinde atrofi şekillendirirken flutamid uygulamasının düzeltici etkilerinin olduğu gözlemlenmiştir. Bu çalışmada bir androjen reseptörü olan flutamid ile dişi ratların üreme fonksiyonları arasındaki ilişkinin daha ilerki çalışmalara kaynak oluşturabileceği görüşündeyiz. Anahtar kelimeler: Flutamid, Anti-androjen, Ovarektomi, Uterus histolojisi, Vücut ağırlığı.

References

  • Smith EP, Boyd J, Frank GR, Takahashi H. Estrogen resistance caused by a mutation in the estrogen receptor gene in a man. N Engl J Med 1994; 331:1088-89.
  • Pelletier G, Labrie C, Labrie F. Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 2000; 165: 359-70.
  • Weihua Z, Saji S, Makinen S, Cheng G. Estrogen receptor beta, a modulator of ER alpha in the uterus. Proc Natl Acad 2000; 97: 5936-41.
  • Barrett Connor R, Young R, Notelovitz M, Sullivan J. A two-year double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. J Reprod Med 1999; 44:1012-20.
  • Beri R, Kumar N, Savage T, Benalcazar L, Sundaram K. Estrogenic and progestational activity of 7α-methyl-19-nortestosterone,a synthetic androgen. J Steroid Biochem Mol Biol 1998; 67: 275-83.
  • Sahlin L, Norstedt G, Eriksson H.Androgen regulation of the insulin- like growth factor,and the estrogen receptor in rat uterus and liver.J Steroid Biochem Mol Biol 1994; 51: 57-66.
  • Giannopoulos G.Binding of testosterone to cytoplasmic components of the immature rat uterus.Biochem Biophys Res Commun 1971; 44: 943-51.
  • Sahlin L, Wang H, Masironi B,Holmgren A, Eriksson H.Regulation of thioredoxin mRNA in the rat uterus by gonadal steroids. J Steroid Biochem Mol Biol 1999; 68: 203-09.
  • Jones RC, Edgren RA. The effects of various steroids on the vaginal histology in the rat. Fertil Steril 1973; 24: 284-91.
  • Okazaki K, Imazawa T, Nakamura H, Furukawa F, Nishikawa A. A repeated 28 day oral dose toxicity study of 17α-methyltestosterone in rats, based on the 'Enhanced OELD Test Guideline 407' for screening the endocrine- disrupting chemicals.Arch Toxical 2002; 75: 635-42.
  • Espuna G, Chuzel F, Esch GP, Pallen C, Bars R. Detection of endocrine effects, an enhaced OECD Test Guideline 407, Study with methyltestosterone.Toxical Sci 2002; 66:276.
  • Neumann F, Graf KJ, Hasan SH. Central actions of antiandrogens. In: L Martini and M Motta (eds). Androgens and antiandrogens, Raven press, Newyork. 1977; 163-77.
  • Neri R.O. Studies on the biology and mechanism of action of nonsteroidal antiandrogens. In: L Martini and M Motta (eds). Androgens and antiandrogens, Raven press, Newyork. 1977; 179-88.
  • Dukes M, Furr JA, Hughes LR. Nonsteroidal progestins and antiprogestins related to flutamide. Steroids 2000; 65: 725-31.
  • Pazo S.F., Sanchez F.F., Balsa J.A. Mechanisms of reduced body growth in the pubertal feminized male rat. Pediatr Res 2000; 48: 96-103.
  • Nguyen P.G., Duman H.J., Siliart B.S. Effects of dietary fat and energy on body weight and composition after gonadectomy in cats. Am J Vet Res 2004; 65: 1708-13.
  • Gray LE., Ostby JS. Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. Toxicol Appl Pharmacol 1994; 129:46-52.
  • Haskell CM. Cancer treatment, 3 rd ed. Philadelphia: WB Saunders Co. 1990; 96.
  • Jellinck PH., Newcombe A.M. Androgen receptor-mediated inhibition of oestrogen- ınduced uterine peroxidase. J Steroid Biochem 1983; 19:1713-17.
  • Karnam RP. Pao LW. Calogero D. Effects of surgıcal ovariectomy on rat salivary gland function. Archs oral Biol 1993; 38: 779-84.
  • Neter J, Wasserman W, Ahitmore GA. Applied Statistics. Boston: Allyn and Bacon 1982; 544- 72.
  • Taguchi O, Cunha GR, Robboy SJ. Experimental study of the effect of diethylstilbestrol on the development of the human female reproductive tract. Biol Res Pregnancy 1983; 4: 56
  • Fisher B, Redmond B, Brown A. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol 1986; 4: 459.
  • Dukes M, Furr JA, Hughes LR. Nonsteroidal progestins and antiprogestins related to flutamide. Steroids 2000;65 :725-31.
  • Schmidt WN, Katzenellen BS. Androgen-uterine interactions: an assessment of androgen interaction with the testosterone and estrogen receptor systems and stimulation of uterine growth and progesterone receptor synthesis. Moll Cell Endocrinol 1979; 15: 91-108.
  • Chandrasekhar Y, Armstrong DT. Regulation of uterine progesterone receptors by the nonsteroidal antiandrogen hydroxyflutamide. Biol Reprod 1991; 45: 78-81.
  • Basson R. Female sexual response the role of drugs in the management of sexual dysfunction. Obstet Gynecol 2001; 98:350-53.
  • Reznikov AG, Sinitsyn PV, Tarasenko LV. Neuroendocrine mechanisms of development of experimental hyperandrogen induced anovulation. Neurosci Behav Physiol 2003; 33: 773-6.
  • Kaori M, Setsuko Y, Masashi S. Effects of perinatal exposure to flutamide on sex hormone responsiveness in F1 male rats. The Journal of Toxicological Sciences 2003; 3:149-63.
  • Branham SW, Sheehan DM, Zehr DR. Inhibition of rat uterine gland genesis by tamoxifen. Endocrinol 1985; 117: 2238.
  • Branham SW, Sheehan DM, Zehr DR. The postnatal ontogeny of rat uterine glands and age related effects of 17 β estradiol. Endocrinol 1985; 117: 2229.
  • Kent J. Development of the infantile mouse uterus: the effect of stilbestrol. J Reprod Fertil 1975; 43:367
  • Clark JH, Mc Cormack SA, Kling R. Effect of clomiphene and other triphenylethylene derivatives on the reproductive tract in the rat and baboon. In: Lacobelli S. Hormones and Cancer 1980; 295.
  • Park SM, Park CH, Wha JD. Ahigh carbohydrate diet induces insulin resistance through decreased glucose utilization in ovariectomized rats. Korean J Intern Med 2004; 19: 87-92.
  • Blaustein JD, Gentry RT, Roy EJ. Effects of ovariectomy and estradiol on body weght and food intake in gold thioglucose treated mice. Physiol Behav 1976; 17: 1027-30.
  • Retra RN, Wenndy NJ, Joseph H. Developmental exposure to DES alters uterine response to estrogens in prepubescent mice: low versus high dose effects. Reprod Toxicol 2004; 18: 399-06.
  • Sutherland MK, Brady H, Gayo LM. Effects of SP 500263, a novel selective estrogen receptor modulator on bone, uterus and serum cholesterol in the ovariectomized rat. Calcif Tissue Int 2003; 72: 710-16.
  • Saruhan BG., Nergiz Y. Histological Effect of Estrogens and Anti-estrogens on uterinal epithelium in estrogen deficiency induced rats. Journal of Dicle Medicine 2002; 29: 1-2.
  • Saruhan BG., Nergiz Y. Histological Effect of Estrogens and Anti-estrogens on vaginal epithelium in estrogen deficiency induced rats. The Chamber of Medicine of Istanbul, Journal of Clinical Development 2003; 16: 1-5.
  • Corresponding Author
  • Dr. BernaGüney SARUHAN
  • Departments of Histology and Embryology,
  • Veterinary Medicine Faculty, University of Dicle, Diyarbakir
  • Tel : +90 412 248 8020-8627
  • Tel : +90 537-798 8616
  • E-Mail : bsaruhan@dicle.edu.tr
There are 46 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Berna Güney Saruhan This is me

Davut Özbağ This is me

Nurullah Özdemir This is me

Yakup Gümüşalan This is me

Publication Date August 1, 2006
Published in Issue Year 2006 Volume: 13 Issue: 4

Cite

APA Saruhan, B. G., Özbağ, D., Özdemir, N., Gümüşalan, Y. (2006). Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması. Journal of Turgut Ozal Medical Center, 13(4), 221-226.
AMA Saruhan BG, Özbağ D, Özdemir N, Gümüşalan Y. Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması. J Turgut Ozal Med Cent. August 2006;13(4):221-226.
Chicago Saruhan, Berna Güney, Davut Özbağ, Nurullah Özdemir, and Yakup Gümüşalan. “Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı Ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması”. Journal of Turgut Ozal Medical Center 13, no. 4 (August 2006): 221-26.
EndNote Saruhan BG, Özbağ D, Özdemir N, Gümüşalan Y (August 1, 2006) Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması. Journal of Turgut Ozal Medical Center 13 4 221–226.
IEEE B. G. Saruhan, D. Özbağ, N. Özdemir, and Y. Gümüşalan, “Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması”, J Turgut Ozal Med Cent, vol. 13, no. 4, pp. 221–226, 2006.
ISNAD Saruhan, Berna Güney et al. “Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı Ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması”. Journal of Turgut Ozal Medical Center 13/4 (August 2006), 221-226.
JAMA Saruhan BG, Özbağ D, Özdemir N, Gümüşalan Y. Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması. J Turgut Ozal Med Cent. 2006;13:221–226.
MLA Saruhan, Berna Güney et al. “Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı Ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması”. Journal of Turgut Ozal Medical Center, vol. 13, no. 4, 2006, pp. 221-6.
Vancouver Saruhan BG, Özbağ D, Özdemir N, Gümüşalan Y. Ovarektomize Ratlarda Flutamid Uygulamasının Vücut Ağırlığı ve Uterus Histolojisi Üzerine Etkilerinin Karşılaştırılması. J Turgut Ozal Med Cent. 2006;13(4):221-6.