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17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi

Year 2018, Volume: 11 Issue: 4, 374 - 384, 15.12.2018
https://doi.org/10.30607/kvj.428131

Abstract



Çalışma farklı doz ve
sürelerde uygulanan 17ß-östradiolün ovaryumları çıkarılmış sıçanlarda spontan
myometriyal kasılımlar üzerine etkisinin belirlenmesi amaçlamaktadır.
Araştırmada 3-6 aylık ve ortalama 270 ± 20 g ağırlığında, 72 adet Sprague
Dawley cinsi dişi sıçanlar kullanılmıştır. 
Sıçanlar, her grupta 18 sıçan bulunacak şekilde, kontrol (Ov) ve 3
deneme gurubuna (östrojen) ayrılmıştır. Kontrol grubuna günlük olarak kas içi
susam yağı enjeksiyonları yapılmış (0,2 ml), birinci deneme grubundaki
sıçanlara günlük 25 µg 17ß-östradiol, ikinci deneme gurubundaki sıçanlara
günlük 50 µg 17ß- östradiol, ve üçüncü deneme gurubundaki sıçanlara günlük 100
µg 17ß-östradiol kas içi uygulanmıştır. Her grup kendi arasında 3 alt gruba
ayrılarak 18, 90 ve 162. saatlerde 6’şar hayvan genel ötenazi yapılmıştır.
Nitrik oksitin etkinliğinin belirlenmesi amacıyla L-Arginin SNP ve L-NNA
(Nitro-N-Arginin) uygulaması yapıldı. Alınan uterus örneklerinden elde edilen
doku kesitlerinde cGMP-PK1 ekspirasyonunu göstermek için immunohistokimyasal
yöntemle boyandı.         Uygulama sonrası
östrojen verilen gruplarda spontan myometriyal kasılımların şiddeti, östrojenin
dozuna ve süresine bağlı olarak arttı. Ayrıca, östrojenin L-arginin-NOS-NO-cGMP
yolunun etkinliğini engellediği belirlendi. Östrojenin uterusta bulunan
longiditunal düz kaslarda cGMP-PK1 ekspirasyonu üzerine etkisinin bulunmadığı
görüldü. Sonuç olarak östrojenin doza ve süreye bağımlı olarak uterus
kasılımlarının şiddetini artırırken, L-Arginin-NOS-NO- cGMP-PK1 yolunun
etkinliğini engellediği fakat bu engellenmenin cGMP-PK1 üzerinden olmadığı
belirlenmiştir.

References

  • Abramowicz JS, Archer DF. Uterine endometrial peristalsis: a trans-vaginal ultrasound study. Fertil Steril. 1990; 54: 451–454.
  • Ahern GP, Hsu SF, Jackson MB. Direct actions of nitric oxide on rat neurohypophysial KCa channels. J Physiol (Lond). 1999; 520: 165–176.
  • Ann Word R, Cornwell LT. Regulation of cGMP-induced relaxation and cGMP-dependent protein kinase in rat myometrium during pregnancy, Am J Physiol. 1998; 43: C748 – C756.
  • Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme, Proc Nat Acad Sci USA. 1990; 87: 682–685.
  • Buhimschi IA, Yallampali C, Buhimschi CS, Saade GR, Garfield RE. Distinct regulation of nitric oxide and cyclic guanosine monophosphate production by steroid hormones in the rat uterus. Mol Human Reprod. 2000; 6:404-414.
  • Buhimschi IA, Yallampali C, Dong YL, Garfield RE. Involvement of a nitric-oxide guanosine monophosphate pathway in control of human uterine contractility during pregnancy. Am J Obstet Gynecol. 1995; 172: 1577–1584.
  • Bulbul A, Altunbas K, Sevimli A, Celik HA. The effects of ovarian steroids on myometrial contractions in ovariectomized rats. Rev Med Vet. 2007; 158: 556-561.
  • Bülbül A, Bülbül T, Özdemir V, Akosman MS, Ulutaş E, Yilmaz O. Biphasic effect of nitric oxide on development of ovarian primordial and primary follicles in laying quail. European Poultry Science. 2015a; 79-90.
  • Bülbül A, Bülbül T, Sevimli A, Yilmaz O. The effect of dietary supplementation of nitric oxide donor and inhibitor on nNOS expression in and motility of the small intestine of broilers. Biotechnic & Histochemistry. 2013; 88(5): 258-266.
  • Bulbul A, Yagci A, Altunbas K, Sevimli A, Celik HA, Karadeniz A, Akdağ E. The role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats. Theriogenology. 2007; 68: 1156-1168.
  • Bülbül T, Akosman MS, Yilmaz O, Ulutaş E, Bülbül A. Supplementary dietary nitric oxide donor (sodium nitroprusside) or inhibitor (NG-nitro-l-arginine methyl ester) depressed growth performance and ovarian primordial and primary follicles in Japanese quail (Coturnix coturnix japonica) in a dose-dependent manner. British Poultry Science. 2015b; 56(1): 113-120.
  • Bülbül T, Özdemir V, Bülbül A, Ulutaş E. The effect of dietary L-arginine intake on the level of antibody titer, the relative organ weight and colon motility in broilers. Polish Journal of Veterinary Sciences. 2014; 17(1): 1800-1805., Doi: 10.2478/pjvs-2014-0015
  • Buxton IL. Regulation of Uterine Function: a Biochemical Conundrum in the Regulation of Smooth Muscle Relaxation. Mol. Pharmacol. 2004; 65: 1051–1059.
  • Buxton IL, Kaiser RA, Malmquist NA, Tichenor S. NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP. Br J Pharmacol.2001; 134: 206–214.
  • Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. 2000; 21: 514-550 .
  • Cornwell TL, Li J, Sellak H, Miller RT, Word RA. Reorganization of myofilament proteins and decreased cGMP-dependent protein kinase in the human uterus during pregnancy. J Clin Endocrinol Metabol. 2001; 86: 3981-3988.
  • Eckman DM, Weinert JS, Buxton IL, Keef KD. Cyclic GMP independent relaxation and hyperpolarization with acetylcholine in guinea pig coronary artery. Br J Pharmacol.1994; 111: 1053–1060.
  • Forstermann U, Schmidt HHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F. Isoforms of nitric oxide synthase characterization and purification from different cell types. Biochem Pharmacol. 1991; 42: 1849-1857.
  • Gart P. Human Pharmacology, ed: Taylor & Francis, New York. 2001; Pp: 107-109.
  • Gordan PL, Jenkins SL, Wentworth RA, Nathanielsz PW. Effect of in vivo estradiol administration to bilaterally ovariectomized rats on in vitro myometrial responsiveness to prostaglandin F2alpha and oxytocin. Biol Repr. 1977; 57:597–601.
  • Gordon AM, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev. 2000; 80:853–924.Harder DR, Coulson PB. Estrogen receptors and effect of estrogen on membrane electrical properties of coronary vascular smooth muscle. J Cell Physiol. 1979; 100:375–382.
  • Hoffmann P, Stanke-Labesque F, Fanchin R, Dilaï N, Pons JC, Ayoubi JM. Effects of L-arginine and sodium nitroprusside on the spontaneous contractility of human non-pregnant uterus. Hum Reprod. 2003; 18: 148-151.
  • Izumi H, Ichihara J, Uchiumi Y, Shirakawa K. Gestational changes in mechanical properties of skinned muscle tissues of human myometrium. Am J Obstet Gynecol. 1990; 163: 638–647.
  • Izumi H, Yallampalli C, Garfield RE. Gestational changes in L-arginine-induced relaxation of pregnant rat and human myometrial smooth muscle, Am J Obst Gynecol. 1993; 169: 1327–1337.
  • Kuenzli KA, Buxton IL, Bradley ME. Nitric oxide regulation of monkey myometrial contractility. Br J Pharmacol. 1998; 124: 63–68.
  • Langrehr JM, Dull KE, Ochoa JB, Billiar TR, Ildstad ST, Schraut WH, Simmons RL, Hoffman RA. Evidence that nitric oxide production by in vivo allosensitized cells inhibits the development of allospecific CTL. Transplantation. 1992; 53: 632-640.
  • Lederman SA, Rosso P. Steroid hormone changes in pregnant rats. www.taxtexts.com/SteroidPaper.PDF. 2004; 1-17.
  • Lincoln TM, Cornwell TL. (1993) Intracellular cyclic GMP receptor proteins. FASEB J. 1993; 7: 328–338.
  • Mazzone JN, Kaiser RA, Buxton IL. Calcium-activated potassium channel expression in human myometrium: effect of pregnancy. Proc West Pharmacol Soc. 2002; 45: 184–186.
  • Misirlioglu D, Nak D, Sevimli A, Nak Y, Ozyigit MO, Akkoc A, Cangul IT. Steroid receptor expression and HER-2/neu (c-erbB-2) oncoprotein in the uterus of cats with cystic endometrial hyperplasia-pyometra complex. J Vet Med A Physiol Pathol Clin Med. 2006; 53:225-229.
  • Oike K, Ishihara K, Kikuchi S. A study on the endometrial movement and serum hormonal level in connection with uterine contraction, Nippon Sanka Fujinka Gakkai Zasshi. 1990; 42: 86–92.
  • Petrocelli T, Lye SJ. Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen and progesterone. Endocrinol. 1993; 133: 284-290.
  • Pinilla L, Gonzalez D, Tena-Sempere M, Aguilar E. Nitric oxide (NO) stimulates gonadotropin secretion in vitro through a calcium-dependent, cGMP independent mechanism. Neuroendocrinology. 1998; 68: 180–186.
  • Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J, Ulrich U, van der Ven H, Wardelmann E, van der Ven K. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Mol Hum Reprod. 2004; 10: 339–346.
  • Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, Lincoln TM, Mendelsohn ME. Regulation of myosin phosphatase by a specific interaction with cGMP-dependent protein kinase Iα. Science. 1999; 286: 1583–1587.
  • Trottier G, Triggle CR, O’Neill SK, Loutzenhiser R. Cyclic GMP-dependent and cyclic GMP-independent actions of nitric oxide on the renal afferent arteriole. Br J Pharmacol. 1998; 125: 563–569.
  • Vedernikov YP, Hartke JR, Long MA. Sex hormone effects in non-pregnant rat and human myometrium. European J Obstet Gynecol Reprod Biol. 2003; 108: 59-66.
  • Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA. 1994; 91: 5212–5216.
  • Weiss G. Endocrinology of parturition, J Clin Endocrinol Metabol. 2000; 12: 4421-4425.
  • Word RA, Cornwell TL. Regulation of cGMP-induced relaxation and cGMP-dependent protein kinase in rat myometrium during pregnancy. Am J Physiol. 1998; 274: 748–756.
  • Yallampali C, Garfield RE, Byam-Smith M. Nitric oxide inhibits uterine contractility during pregnancy but not during delivery. Endocrinol. 1993; 133: 1899–1902.Yallampali C, Izumi H, Byam-Smith M, Garfield RE. An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy. Am J Obstet Gynecol. 1994; 170: 175–185.

Effects of 17β-Estradiol on Spontaneous Myometrial Contractions in Overiectomized Rats

Year 2018, Volume: 11 Issue: 4, 374 - 384, 15.12.2018
https://doi.org/10.30607/kvj.428131

Abstract

The aim of this study was to evaluate the effect of
injecting different doses and time intervals of 17β-estradiol on spontaneous
myometrial contractions of ovariectomized rats. Three to 6 months old 72 female
Sprague Dawley rats, weighing 270 ± 20 g, were used in the current study. The
ovariectomized rats were randomly assigned to a control (Ov) and three
experimental groups (17β-estradiol injected) of 18 rats each. Rats in the Ov
group received daily sesame oil (0.2 ml, IM), whereas each rat in the three
experimental groups was treated with daily 25, 50 and 100 μg estradiol (IM),
respectively. Each group was further divided into 3 subgroups: 6 rats in each
group were sacrificed by cervical dislocation at 18, 90 and 162 hr. In order to
determine endogenous nitric oxide activity, the L-arginine solution was
used.  Sodium nitroprusside (SNP) was
used for evaluation of the exogenous nitric oxide pathway. In addition, L-NNA
(nitro-N-arginine) treatment was applied in order to determine the effect of
endogenous NO at the receptor level. Immunohistochemical evaluation was
performed to determine the cGMP-PK1 expression from the uterus samples. In the
current study, estrogen treatment increased spontaneous myometrial contraction
in a dose and time-dependent manner. Moreover, estrogen treatments inhibited
L-arginine-NOS-NO-cGMP pathway. On the other hand, estrogen failed to have any
effect on cGMP-PK1 expression in uterine longitudinal smooth muscles.  Thus, 17β-estradiol treatments increased the
uterine smooth muscle cell contractions. The treatments also inhibited
L-Arginine-NOS-NO-cGMP-PK1 pathway. However, our results indicated that
17β-estradiol did not show its effect through cGMP-PK1.

References

  • Abramowicz JS, Archer DF. Uterine endometrial peristalsis: a trans-vaginal ultrasound study. Fertil Steril. 1990; 54: 451–454.
  • Ahern GP, Hsu SF, Jackson MB. Direct actions of nitric oxide on rat neurohypophysial KCa channels. J Physiol (Lond). 1999; 520: 165–176.
  • Ann Word R, Cornwell LT. Regulation of cGMP-induced relaxation and cGMP-dependent protein kinase in rat myometrium during pregnancy, Am J Physiol. 1998; 43: C748 – C756.
  • Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme, Proc Nat Acad Sci USA. 1990; 87: 682–685.
  • Buhimschi IA, Yallampali C, Buhimschi CS, Saade GR, Garfield RE. Distinct regulation of nitric oxide and cyclic guanosine monophosphate production by steroid hormones in the rat uterus. Mol Human Reprod. 2000; 6:404-414.
  • Buhimschi IA, Yallampali C, Dong YL, Garfield RE. Involvement of a nitric-oxide guanosine monophosphate pathway in control of human uterine contractility during pregnancy. Am J Obstet Gynecol. 1995; 172: 1577–1584.
  • Bulbul A, Altunbas K, Sevimli A, Celik HA. The effects of ovarian steroids on myometrial contractions in ovariectomized rats. Rev Med Vet. 2007; 158: 556-561.
  • Bülbül A, Bülbül T, Özdemir V, Akosman MS, Ulutaş E, Yilmaz O. Biphasic effect of nitric oxide on development of ovarian primordial and primary follicles in laying quail. European Poultry Science. 2015a; 79-90.
  • Bülbül A, Bülbül T, Sevimli A, Yilmaz O. The effect of dietary supplementation of nitric oxide donor and inhibitor on nNOS expression in and motility of the small intestine of broilers. Biotechnic & Histochemistry. 2013; 88(5): 258-266.
  • Bulbul A, Yagci A, Altunbas K, Sevimli A, Celik HA, Karadeniz A, Akdağ E. The role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats. Theriogenology. 2007; 68: 1156-1168.
  • Bülbül T, Akosman MS, Yilmaz O, Ulutaş E, Bülbül A. Supplementary dietary nitric oxide donor (sodium nitroprusside) or inhibitor (NG-nitro-l-arginine methyl ester) depressed growth performance and ovarian primordial and primary follicles in Japanese quail (Coturnix coturnix japonica) in a dose-dependent manner. British Poultry Science. 2015b; 56(1): 113-120.
  • Bülbül T, Özdemir V, Bülbül A, Ulutaş E. The effect of dietary L-arginine intake on the level of antibody titer, the relative organ weight and colon motility in broilers. Polish Journal of Veterinary Sciences. 2014; 17(1): 1800-1805., Doi: 10.2478/pjvs-2014-0015
  • Buxton IL. Regulation of Uterine Function: a Biochemical Conundrum in the Regulation of Smooth Muscle Relaxation. Mol. Pharmacol. 2004; 65: 1051–1059.
  • Buxton IL, Kaiser RA, Malmquist NA, Tichenor S. NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP. Br J Pharmacol.2001; 134: 206–214.
  • Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. 2000; 21: 514-550 .
  • Cornwell TL, Li J, Sellak H, Miller RT, Word RA. Reorganization of myofilament proteins and decreased cGMP-dependent protein kinase in the human uterus during pregnancy. J Clin Endocrinol Metabol. 2001; 86: 3981-3988.
  • Eckman DM, Weinert JS, Buxton IL, Keef KD. Cyclic GMP independent relaxation and hyperpolarization with acetylcholine in guinea pig coronary artery. Br J Pharmacol.1994; 111: 1053–1060.
  • Forstermann U, Schmidt HHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F. Isoforms of nitric oxide synthase characterization and purification from different cell types. Biochem Pharmacol. 1991; 42: 1849-1857.
  • Gart P. Human Pharmacology, ed: Taylor & Francis, New York. 2001; Pp: 107-109.
  • Gordan PL, Jenkins SL, Wentworth RA, Nathanielsz PW. Effect of in vivo estradiol administration to bilaterally ovariectomized rats on in vitro myometrial responsiveness to prostaglandin F2alpha and oxytocin. Biol Repr. 1977; 57:597–601.
  • Gordon AM, Homsher E, Regnier M. Regulation of contraction in striated muscle. Physiol Rev. 2000; 80:853–924.Harder DR, Coulson PB. Estrogen receptors and effect of estrogen on membrane electrical properties of coronary vascular smooth muscle. J Cell Physiol. 1979; 100:375–382.
  • Hoffmann P, Stanke-Labesque F, Fanchin R, Dilaï N, Pons JC, Ayoubi JM. Effects of L-arginine and sodium nitroprusside on the spontaneous contractility of human non-pregnant uterus. Hum Reprod. 2003; 18: 148-151.
  • Izumi H, Ichihara J, Uchiumi Y, Shirakawa K. Gestational changes in mechanical properties of skinned muscle tissues of human myometrium. Am J Obstet Gynecol. 1990; 163: 638–647.
  • Izumi H, Yallampalli C, Garfield RE. Gestational changes in L-arginine-induced relaxation of pregnant rat and human myometrial smooth muscle, Am J Obst Gynecol. 1993; 169: 1327–1337.
  • Kuenzli KA, Buxton IL, Bradley ME. Nitric oxide regulation of monkey myometrial contractility. Br J Pharmacol. 1998; 124: 63–68.
  • Langrehr JM, Dull KE, Ochoa JB, Billiar TR, Ildstad ST, Schraut WH, Simmons RL, Hoffman RA. Evidence that nitric oxide production by in vivo allosensitized cells inhibits the development of allospecific CTL. Transplantation. 1992; 53: 632-640.
  • Lederman SA, Rosso P. Steroid hormone changes in pregnant rats. www.taxtexts.com/SteroidPaper.PDF. 2004; 1-17.
  • Lincoln TM, Cornwell TL. (1993) Intracellular cyclic GMP receptor proteins. FASEB J. 1993; 7: 328–338.
  • Mazzone JN, Kaiser RA, Buxton IL. Calcium-activated potassium channel expression in human myometrium: effect of pregnancy. Proc West Pharmacol Soc. 2002; 45: 184–186.
  • Misirlioglu D, Nak D, Sevimli A, Nak Y, Ozyigit MO, Akkoc A, Cangul IT. Steroid receptor expression and HER-2/neu (c-erbB-2) oncoprotein in the uterus of cats with cystic endometrial hyperplasia-pyometra complex. J Vet Med A Physiol Pathol Clin Med. 2006; 53:225-229.
  • Oike K, Ishihara K, Kikuchi S. A study on the endometrial movement and serum hormonal level in connection with uterine contraction, Nippon Sanka Fujinka Gakkai Zasshi. 1990; 42: 86–92.
  • Petrocelli T, Lye SJ. Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen and progesterone. Endocrinol. 1993; 133: 284-290.
  • Pinilla L, Gonzalez D, Tena-Sempere M, Aguilar E. Nitric oxide (NO) stimulates gonadotropin secretion in vitro through a calcium-dependent, cGMP independent mechanism. Neuroendocrinology. 1998; 68: 180–186.
  • Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J, Ulrich U, van der Ven H, Wardelmann E, van der Ven K. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Mol Hum Reprod. 2004; 10: 339–346.
  • Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, Lincoln TM, Mendelsohn ME. Regulation of myosin phosphatase by a specific interaction with cGMP-dependent protein kinase Iα. Science. 1999; 286: 1583–1587.
  • Trottier G, Triggle CR, O’Neill SK, Loutzenhiser R. Cyclic GMP-dependent and cyclic GMP-independent actions of nitric oxide on the renal afferent arteriole. Br J Pharmacol. 1998; 125: 563–569.
  • Vedernikov YP, Hartke JR, Long MA. Sex hormone effects in non-pregnant rat and human myometrium. European J Obstet Gynecol Reprod Biol. 2003; 108: 59-66.
  • Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA. 1994; 91: 5212–5216.
  • Weiss G. Endocrinology of parturition, J Clin Endocrinol Metabol. 2000; 12: 4421-4425.
  • Word RA, Cornwell TL. Regulation of cGMP-induced relaxation and cGMP-dependent protein kinase in rat myometrium during pregnancy. Am J Physiol. 1998; 274: 748–756.
  • Yallampali C, Garfield RE, Byam-Smith M. Nitric oxide inhibits uterine contractility during pregnancy but not during delivery. Endocrinol. 1993; 133: 1899–1902.Yallampali C, Izumi H, Byam-Smith M, Garfield RE. An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy. Am J Obstet Gynecol. 1994; 170: 175–185.
There are 41 citations in total.

Details

Primary Language Turkish
Journal Section RESEARCH ARTICLE
Authors

Özlem Yıldız Gülay

Aziz Bülbül This is me

Publication Date December 15, 2018
Acceptance Date August 31, 2018
Published in Issue Year 2018 Volume: 11 Issue: 4

Cite

APA Yıldız Gülay, Ö., & Bülbül, A. (2018). 17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi. Kocatepe Veterinary Journal, 11(4), 374-384. https://doi.org/10.30607/kvj.428131
AMA Yıldız Gülay Ö, Bülbül A. 17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi. kvj. December 2018;11(4):374-384. doi:10.30607/kvj.428131
Chicago Yıldız Gülay, Özlem, and Aziz Bülbül. “17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi”. Kocatepe Veterinary Journal 11, no. 4 (December 2018): 374-84. https://doi.org/10.30607/kvj.428131.
EndNote Yıldız Gülay Ö, Bülbül A (December 1, 2018) 17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi. Kocatepe Veterinary Journal 11 4 374–384.
IEEE Ö. Yıldız Gülay and A. Bülbül, “17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi”, kvj, vol. 11, no. 4, pp. 374–384, 2018, doi: 10.30607/kvj.428131.
ISNAD Yıldız Gülay, Özlem - Bülbül, Aziz. “17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi”. Kocatepe Veterinary Journal 11/4 (December 2018), 374-384. https://doi.org/10.30607/kvj.428131.
JAMA Yıldız Gülay Ö, Bülbül A. 17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi. kvj. 2018;11:374–384.
MLA Yıldız Gülay, Özlem and Aziz Bülbül. “17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi”. Kocatepe Veterinary Journal, vol. 11, no. 4, 2018, pp. 374-8, doi:10.30607/kvj.428131.
Vancouver Yıldız Gülay Ö, Bülbül A. 17β-Östradiolün Overioktomize Ratlarda Spontan Myometriyal Kasılımlar Üzerine Etkisi. kvj. 2018;11(4):374-8.

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