Nesfatin-1 ve Kisspeptin Antagonisti P234’ün Ovaryum Folikül Gelişimine Etkileri
Yıl 2022,
Cilt: 5 Sayı: 2-3, 79 - 87, 13.03.2023
Zafer Şahin
,
Gökhan Cüce
,
Mete Özcan
,
Sinan Canpolat
,
Z Işık Solak Görmüş
,
Selim Kutlu
,
Haluk Keleştimur Keleştimur
Öz
Amaç: Araştırmamızda nesfatin-1 ve kisspeptin reseptör antagonistinin sıçanlarda ovaryum foliküllerinin gelişim sayıları üzerine etkilerinin belirlenmesi amaçlanmıştır.
Gereç ve Yöntemler: Çalışmamızda 21 günlük sütten kesilmiş Spraque-Dawley dişi yavru sıçanlar kullanılmıştır. Hayvanlara intraserebroventriküler (ICV) enjeksiyon için kanüller anestezi altında takıldıktan sonra, 23. günden 60. güne kadar nesfatin-1, p234 ve nesfatin-1+p234 günlük santral (intraserebroventrikülar (icv)) olarak enjekte edilmiştir. Enjeksiyonlar tamamlanınca, hayvanlar diöstrüs dönemindeyken deneyler sonlandırılmıştır. Elde edilen ovaryum örneklerinde folikül sayımı yapılmıştır.
Bulgular: Çalışmamızda uzun süreli kronik santral kisspeptin antagonisti p234 enjeksiyonunun ovaryum folikül gelişiminde bir düşüşe yol açtığı belirlendi. Benzer sonuç nesfatin-1+p234 grubu için de geçerliydi.
Sonuç: Elde ettiğimiz bulgulara göre ovaryum folikül gelişiminde kisspeptin reseptör (Kiss1r) antagonisti nesfatin-1’in etkisini azalttığı söylenebilir. Bu durum nesfatin-1’in kisspeptin/Kiss1r sinyalleşmesiyle etkileşimi olduğu şeklinde yorumlanabilir. Bununla birlikte sadece p234’ün etkisine bağlı ovaryum folikül sayıları azalmış olabilir.
Kaynakça
- Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature [Internet]. 2006 Oct 1;443(7112):709–12. Available from: http://www.nature.com/articles/nature05162
- Miura K, Titani K, Kurosawa Y, Kanai Y. Molecular cloning of nucleobindin, a novel DNA-binding protein that contains both a signal peptide and a leucine zipper structure. Biochem Biophys Res Commun [Internet]. 1992 Aug;187(1):375–80. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006291X05815037
- Barnikol-Watanabe S, Groß NA, Götz H, Henkel T, Karabinos A, Kratzin H, et al. Human Protein NEFA, a Novel DNA Binding / EF-Hand / Leucine Zipper Protein. Molecular Cloning and Sequence Analysis of the cDNA, Isolation and Characterization of the Protein. Biol Chem Hoppe Seyler [Internet]. 1994 Jan;375(8):497–512. Available from: https://www.degruyter.com/doi/10.1515/bchm3.1994.375.8.497
- Shimizu H, Oh-I S, Hashimoto K, Nakata M, Yamamoto S, Yoshida N, et al. Peripheral Administration of Nesfatin-1 Reduces Food Intake in Mice: The Leptin-Independent Mechanism. Endocrinology [Internet]. 2009 Feb 1;150(2):662–71. Available from: https://academic.oup.com/endo/article/150/2/662/2455552
- García-Galiano D, Navarro VM, Gaytan F, Tena-Sempere M. Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation. J Mol Endocrinol [Internet]. 2010 Nov;45(5):281–90. Available from: https://jme.bioscientifica.com/view/journals/jme/45/5/281.xml
- Garcia-Galiano D, Navarro VM, Roa J, Ruiz-Pino F, Sanchez-Garrido MA, Pineda R, et al. The Anorexigenic Neuropeptide, Nesfatin-1, Is Indispensable for Normal Puberty Onset in the Female Rat. J Neurosci [Internet]. 2010 Jun 9;30(23):7783–92. Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.5828-09.2010
- Kelestimur H, Sahin Z, Bulmus O, Ozcan M, Canpolat S. Kisspeptin Antagonist, Peptide 234, Blocks Both Kisspeptin-10 And Nesfatin-1-Ioduced Luteinizing Hormone Release in The Female Rats. J Sex Med. 2015;12:287.
- Tarumi W, Suzuki N, Takahashi N, Kobayashi Y, Kiguchi K, Sato K, et al. Ovarian toxicity of paclitaxel and effect on fertility in the rat. J Obstet Gynaecol Res [Internet]. 2009 Jun;35(3):414–20. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2009.01023.x
- Inhoff T, Stengel A, Peter L, Goebel M, Taché Y, Bannert N, et al. Novel insight in distribution of nesfatin-1 and phospho-mTOR in the arcuate nucleus of the hypothalamus of rats. Peptides [Internet]. 2010 Feb;31(2):257–62. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0196978109005154
- Roa J, Garcia-Galiano D, Varela L, Sánchez-Garrido MA, Pineda R, Castellano JM, et al. The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System. Endocrinology [Internet]. 2009 Nov 1;150(11):5016–26. Available from: https://academic.oup.com/endo/article/150/11/5016/2455466
- Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A, et al. The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun [Internet]. 2003 Dec;312(4):1357–63. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006291X03024070
- d’Anglemont de Tassigny X, Fagg LA, Dixon JPC, Day K, Leitch HG, Hendrick AG, et al. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci U S A [Internet]. 2007 Jun 19;104(25):10714–9. Available from: https://pnas.org/doi/full/10.1073/pnas.0704114104
- Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al. The GPR54 Gene as a Regulator of Puberty. N Engl J Med [Internet]. 2003 Oct 23;349(17):1614–27. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa035322
- Lapatto R, Pallais JC, Zhang D, Chan Y-M, Mahan A, Cerrato F, et al. Kiss1 −/− Mice Exhibit More Variable Hypogonadism than Gpr54−/− Mice. Endocrinology [Internet]. 2007 Oct 1;148(10):4927–36. Available from: https://academic.oup.com/endo/article/148/10/4927/2501727
- Dungan HM, Gottsch ML, Zeng H, Gragerov A, Bergmann JE, Vassilatis DK, et al. The Role of Kisspeptin GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone. J Neurosci [Internet]. 2007 Oct 31;27(44):12088–95. Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2748-07.2007
- Kauffman AS, Park JH, McPhie-Lalmansingh AA, Gottsch ML, Bodo C, Hohmann JG, et al. The Kisspeptin Receptor GPR54 Is Required for Sexual Differentiation of the Brain and Behavior. J Neurosci [Internet]. 2007 Aug 15;27(33):8826–35. Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2099-07.2007
- Shahed A, Young KA. Differential ovarian expression of KiSS-1 and GPR-54 during the estrous cycle and photoperiod induced recrudescence in Siberian hamsters ( Phodopus sungorus ). Mol Reprod Dev [Internet]. 2009 May;76(5):444–52. Available from: https://onlinelibrary.wiley.com/doi/10.1002/mrd.20972
- Cejudo Roman A, Pinto FM, Dorta I, Almeida TA, Hernández M, Illanes M, et al. Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract. Fertil Steril [Internet]. 2012 May;97(5):1213–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0015028212002531
- Zhang P, Tang M, Zhong T, Lin Y, Zong T, Zhong C, et al. Expression and Function of Kisspeptin during Mouse Decidualization. Wang H, editor. PLoS One [Internet]. 2014 May 15;9(5):e97647. Available from: https://dx.plos.org/10.1371/journal.pone.0097647
- Hu K-L, Zhao H, Chang H-M, Yu Y, Qiao J. Kisspeptin/Kisspeptin Receptor System in the Ovary. Front Endocrinol (Lausanne) [Internet]. 2018 Jan 4;8. Available from: http://journal.frontiersin.org/article/10.3389/fendo.2017.00365/full
Effects of Nesfatin-1 and Kisspeptin Antagonist p234 on Ovarian Follicle Development
Yıl 2022,
Cilt: 5 Sayı: 2-3, 79 - 87, 13.03.2023
Zafer Şahin
,
Gökhan Cüce
,
Mete Özcan
,
Sinan Canpolat
,
Z Işık Solak Görmüş
,
Selim Kutlu
,
Haluk Keleştimur Keleştimur
Öz
Objective: In our study, it was aimed to determine the effects of nesfatin-1 and kisspeptin receptor antagonist on the developmental numbers of ovarian follicles in rats.
Material and Methods: In our study, 21-day-old weaned Spraque-Dawley female baby rats were used. After insertion of cannulas for intracerebroventricular (ICV) injection into animals, from day 23 to day 60, nesfatin-1, p234 and nesfatin-1+p234 were injected daily centrally (intracerebroventricular (icv)). When the injections were completed, the experiments were terminated while the animals were in diestrus. Follicle counts were made in the ovarian samples obtained.
Results: In our study, it was determined that long-term chronic injection of the central kisspeptin antagonist p234 caused a decrease in ovarian follicle development. Similar results were also valid for the nesfatin-1+p234 group.
Conclusion: According to our findings, it can be said that kisspeptin receptor (Kiss1r) antagonist nesfatin-1 reduces the effect of ovarian follicle development. This can be interpreted as nesfatin-1 interacting with kisspeptin/Kiss1r signaling. However, the number of ovarian follicles may have decreased due to the effect of only p234.
Kaynakça
- Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature [Internet]. 2006 Oct 1;443(7112):709–12. Available from: http://www.nature.com/articles/nature05162
- Miura K, Titani K, Kurosawa Y, Kanai Y. Molecular cloning of nucleobindin, a novel DNA-binding protein that contains both a signal peptide and a leucine zipper structure. Biochem Biophys Res Commun [Internet]. 1992 Aug;187(1):375–80. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006291X05815037
- Barnikol-Watanabe S, Groß NA, Götz H, Henkel T, Karabinos A, Kratzin H, et al. Human Protein NEFA, a Novel DNA Binding / EF-Hand / Leucine Zipper Protein. Molecular Cloning and Sequence Analysis of the cDNA, Isolation and Characterization of the Protein. Biol Chem Hoppe Seyler [Internet]. 1994 Jan;375(8):497–512. Available from: https://www.degruyter.com/doi/10.1515/bchm3.1994.375.8.497
- Shimizu H, Oh-I S, Hashimoto K, Nakata M, Yamamoto S, Yoshida N, et al. Peripheral Administration of Nesfatin-1 Reduces Food Intake in Mice: The Leptin-Independent Mechanism. Endocrinology [Internet]. 2009 Feb 1;150(2):662–71. Available from: https://academic.oup.com/endo/article/150/2/662/2455552
- García-Galiano D, Navarro VM, Gaytan F, Tena-Sempere M. Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation. J Mol Endocrinol [Internet]. 2010 Nov;45(5):281–90. Available from: https://jme.bioscientifica.com/view/journals/jme/45/5/281.xml
- Garcia-Galiano D, Navarro VM, Roa J, Ruiz-Pino F, Sanchez-Garrido MA, Pineda R, et al. The Anorexigenic Neuropeptide, Nesfatin-1, Is Indispensable for Normal Puberty Onset in the Female Rat. J Neurosci [Internet]. 2010 Jun 9;30(23):7783–92. Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.5828-09.2010
- Kelestimur H, Sahin Z, Bulmus O, Ozcan M, Canpolat S. Kisspeptin Antagonist, Peptide 234, Blocks Both Kisspeptin-10 And Nesfatin-1-Ioduced Luteinizing Hormone Release in The Female Rats. J Sex Med. 2015;12:287.
- Tarumi W, Suzuki N, Takahashi N, Kobayashi Y, Kiguchi K, Sato K, et al. Ovarian toxicity of paclitaxel and effect on fertility in the rat. J Obstet Gynaecol Res [Internet]. 2009 Jun;35(3):414–20. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2009.01023.x
- Inhoff T, Stengel A, Peter L, Goebel M, Taché Y, Bannert N, et al. Novel insight in distribution of nesfatin-1 and phospho-mTOR in the arcuate nucleus of the hypothalamus of rats. Peptides [Internet]. 2010 Feb;31(2):257–62. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0196978109005154
- Roa J, Garcia-Galiano D, Varela L, Sánchez-Garrido MA, Pineda R, Castellano JM, et al. The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System. Endocrinology [Internet]. 2009 Nov 1;150(11):5016–26. Available from: https://academic.oup.com/endo/article/150/11/5016/2455466
- Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A, et al. The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun [Internet]. 2003 Dec;312(4):1357–63. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006291X03024070
- d’Anglemont de Tassigny X, Fagg LA, Dixon JPC, Day K, Leitch HG, Hendrick AG, et al. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci U S A [Internet]. 2007 Jun 19;104(25):10714–9. Available from: https://pnas.org/doi/full/10.1073/pnas.0704114104
- Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al. The GPR54 Gene as a Regulator of Puberty. N Engl J Med [Internet]. 2003 Oct 23;349(17):1614–27. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa035322
- Lapatto R, Pallais JC, Zhang D, Chan Y-M, Mahan A, Cerrato F, et al. Kiss1 −/− Mice Exhibit More Variable Hypogonadism than Gpr54−/− Mice. Endocrinology [Internet]. 2007 Oct 1;148(10):4927–36. Available from: https://academic.oup.com/endo/article/148/10/4927/2501727
- Dungan HM, Gottsch ML, Zeng H, Gragerov A, Bergmann JE, Vassilatis DK, et al. The Role of Kisspeptin GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone. J Neurosci [Internet]. 2007 Oct 31;27(44):12088–95. Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2748-07.2007
- Kauffman AS, Park JH, McPhie-Lalmansingh AA, Gottsch ML, Bodo C, Hohmann JG, et al. The Kisspeptin Receptor GPR54 Is Required for Sexual Differentiation of the Brain and Behavior. J Neurosci [Internet]. 2007 Aug 15;27(33):8826–35. Available from: https://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2099-07.2007
- Shahed A, Young KA. Differential ovarian expression of KiSS-1 and GPR-54 during the estrous cycle and photoperiod induced recrudescence in Siberian hamsters ( Phodopus sungorus ). Mol Reprod Dev [Internet]. 2009 May;76(5):444–52. Available from: https://onlinelibrary.wiley.com/doi/10.1002/mrd.20972
- Cejudo Roman A, Pinto FM, Dorta I, Almeida TA, Hernández M, Illanes M, et al. Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract. Fertil Steril [Internet]. 2012 May;97(5):1213–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0015028212002531
- Zhang P, Tang M, Zhong T, Lin Y, Zong T, Zhong C, et al. Expression and Function of Kisspeptin during Mouse Decidualization. Wang H, editor. PLoS One [Internet]. 2014 May 15;9(5):e97647. Available from: https://dx.plos.org/10.1371/journal.pone.0097647
- Hu K-L, Zhao H, Chang H-M, Yu Y, Qiao J. Kisspeptin/Kisspeptin Receptor System in the Ovary. Front Endocrinol (Lausanne) [Internet]. 2018 Jan 4;8. Available from: http://journal.frontiersin.org/article/10.3389/fendo.2017.00365/full