The Effects of Kisspeptin System on Ewe Reproduction

Abstract

The Kiss 1 gene, Kiss1 reseptor and kisspeptin peptide system play an important roles in the regulation of reproductive function. Kiss1 gene products 145-amino acid precursor protein cleaved to active kisspeptin forms. The kisspeptin system have important role in the negative and positive feedback mechanism of gonadal steroids. Total kisspeptin cell number appears to differ between the arcuate and preoptic region of the hypothalamus which these cells number change with season and phases of oestrus. Kiss1 neurons express other neuropeptides such as neurokinin B and dynorphin, which may play important roles involving steroids feedback control mechanisms. The ability of kisspeptin to stimulate gonadotropin secretion and synchronization ovulation, alternatives to design new synchronization protocols aimed at improving fertility

Keywords

• GnRH Kisspeptin Ewe Ovulation Reproduction

Kisspeptin Sisteminin Koyun Reprodüksiyonu Üzerine Etkileri

Abstract

Kiss1 geni, kiss1 reseptörü ve kisspeptin peptid sistemi reprodüktif fonksiyonların düzenlenmesinde önemli rol oynamaktadır. Kiss1 gen ürünü olan 145 amino asit yapısına sahip prekürsör proteini aktif kisspeptin formlarına dönüşmektedir. Kisspeptin sisteminin gonodal steroitlerin negatif ve pozitif feedback mekanizmasında önemli rolleri vardır. Hipotalamus’un arkuat ve preoptik bölgelerindeki toplam kisspeptin hücre sayısı farklı olup, bu hücre sayıları mevsime ve östrus dönemlerine göre değişmektedir. Kiss1 nöronları nörokinin B ve dinofrin gibi steroitlerin feedback kontrol mekanizmasında önemli rolleri olan diğer nöropeptidlerin ekspresyonunu gerçekleştirmektedir. Kisspeptin gonadotropin sekrasyonunu uyarıp ovulasyonu senkronize edebildiğinden fertiliteyi artıracak yeni senkronizasyon protokollerinin geliştirilmesine alternatif olabilir. ●●● The Effects of Kisspeptin System on Ewe Reproduction S U M M A R Y The Kiss 1 gene, Kiss1 reseptor and kisspeptin peptide system play an important roles in the regulation of reproductive function. Kiss1 gene products 145-amino acid precursor protein cleaved to active kisspeptin forms. The kisspeptin system have important role in the negative and positive feedback mechanism of gonadal steroids. Total kisspeptin cell number appears to differ between the arcuate and preoptic region of the hypothalamus which these cells number change with season and phases of oestrus. Kiss1 neurons express other neuropeptides such as neurokinin B and dynorphin, which may play important roles involving steroids feedback control mechanisms. The ability of kisspeptin to stimulate gonadotropin secretion and synchronization ovulation, alternatives to design new synchronization protocols aimed at improving fertility.

Keywords

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References

1. Backholer K, Bowden M, Gamber K, Bjİrbaek C, Iqbal J, Clarke I.J. 2010a. Melanocortins mimic the effects of leptin to restore reproductive function in lean hypogonadotropic ewes Neuroendocrinology. 91(1): 27-40
2. Backholer K, Smith J.T, Rao A, Pereıra A, Iqbal J, Ogawa S, Lı Q, Clarke I.J. 2010b. Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide y and proopiomelanocortin cells. Endocrinology 151: 2233–2243.
3. Birdane MK, 2012. Kisspeptinin koyunlarda Bazı Reprodüktif Parametrelere Etkisi. Doktora tezi, Afyon Kocatepe Üniversitesi Sağlık Bilimleri Enstitüsü, Afyonkarahisar.
4. Campbell R.E. 2007. Defining the gonadotrophinreleasing hormone neuronal network: transgenic approaches to understanding neurocircuitry J Neuroendocrinol. 19(7): 561
5. Caraty A, Fabrenys C, Delaleu B, Locatellı A, Bruneau G, Karsch, F. 1998. Evidence that the mediobasal hypothalamus is the primary site of action of estradiol in inducing the preovulatory gonadotropin releasing hormone surge in the ewe. Endocrinology. 139: 1752–
6. Caraty A, Smith JT, Lomet D, Ben Saïd S, MorrısseyA, Cognıe J, Doughton B, Barıl G, Brıant C, Clarke IJ. 2007. Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes. Endocrinology. 148(11): 5258-5267.
7. Caraty A, Franceschını I. 2008. Basic aspects of the control of GnRH and LH secretions by kisspeptin: potential applications for better control of fertility in females. Reprod Domest Anim. 43(2): 172-178.
8. Caraty A, Franceschını I, Hoffman GE. 2010. Kisspeptin and the preovulatory gonadotrophin-releasing hormone/luteinising hormone surge in the ewe: basic aspects and potential applications in the control of ovulation J Neuroendocrinol. 22(7): 710-715

9. Castellano JM, Roa J, Luque RM, Dıeguez C, Aguılar E, Pınılla L, Tena-Sempere M. 200 KiSS-1/kisspeptins and the metabolic control of reproduction: physiologic roles and putative physiopathological implications. Peptides 30: 139 –145. Cheng G, Coolen LM, Padmanabhan V, Goodman RL, Lehman MN. 2010. The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep Endocrinology. 151(1): 301-311
10. Christian CA, Moenter SM. (2010). The neurobiology of preovulatory and estradiolinduced gonadotropin-releasing hormone surges. Endocr Rev. 31: 544-77
11. Clarke IJ, Qı Y, Puspıta I, Smith, JT. (2009a). Evidence that RF-amid related peptides are inhibitors of reproduction in mammals. Front Neuroendocrinol. 30(3): 371-378
12. Clarke IJ, Smith JT, Caraty A, Goodman LR, Lehman M. (2009b). Kisspeptin and seasonality in sheep. Peptides 30: 154–163
13. Clarke IJ. (2011). Control of GnRH secretion: One step back. Front Neuroendocrinol 32(3): 367375
14. Clarkson J, Han SK, Lıu X, Lee K, Herbıson AE. (2010). Neurobiological mechanisms underlying kisspeptin activation of gonadotropin-releasing hormone (GnRH) neurons at puberty. Mol Cell Endocrinol 324(1-2): 45-50.
15. Dardente H, Bırnıe M, Lıncoln GA, Hazlerıgg DG. 2008. RFamide-related peptide and its cognate receptor in the sheep: cDNA cloning, mRNA distribution in the hypothalamus and the effect of photoperiod. J Neuroendocrinol. 20(11): 1252-1259.
16. De Roux N, Milgrom E. 2001. Inherited disorders of GnRH and gonadotropin receptors. Mol Cell Endocrinol. 179(1-2):83-7.
17. Dhillo WS, Chaudhrı OB, Thompson EL, Murphy KG, Patterson M, Ramachandran R, Nıjher GK, Amber V, Kokkınos A, Donaldson M, Ghateı MA, Bloom SR. 200 Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J. Clin. Endocrinol. Metab. 92: 3958–3966.
18. Estrada KM, Clay CM, PompoloS, Smith JT, Clarke IJ. 2006. Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/luteinising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback, J. Neuroendocrinol. 18: 806–809
19. Foradorı CD, Coolen LM, Fıtzgerald ME, Skınner DC, Goodman RL, Lehman MN. 200 Colocalization of progesterone receptors in parvicellular dynorphin neurons 41 Greives TJ, Mason AO, Scotti MA, Levine J, Ketterson ED, Kriegsfeld LJ, Demas GE. 200 Environmental control of kisspeptin: implications for seasonal reproduction. Endocrinology. 148(3):1158-66
20. Hameed S, Jayasena C, Dhıllo W. 2011. Kisspeptin and fertility. Journal of Endocrinology 208(2): 97–105.
21. Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawıch SK, Clıfton DK, Steıner RA, Herbison AE. 2005. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci. 25(49):11349-56. Hashizume T, Saıto H, Sawada T, Yaegashı T, Ezzat AA, Sawaı K, Yamashıta T. 2010. Characteristics of stimulation of gonadotropin secretion by kisspeptin-10 in female goats. Anim Reprod Sci. 118(1):37-41.
22. Henry BA, Godıng JW, Tılbrook AJ, Dunshea FR, Clarke IJ. 2001. Intracerebroventricular infusion of leptin elevates the secretion of luteinising hormone without affecting food intake in long-term food-restricted sheep, but increases growth hormone irrespective of bodyweight, J. Endocrinol. 168: 67–77.
23. Hiden U, Bılban M, Knöfler M, Desoye G. 2007. Kisspeptins and the placenta:regulation of trophoblast invasion. Rev Endocr Metab Disord. 8: 31-39.
24. Hill JW, Elmquıst JK, Elıas CF. 2008. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab. 294(5): E827-32.
25. Hori A, Honda S, Asada M, Ohtakı T, Oda K, Watanabe T, Shıntanı Y, Yamada T, Suenaga M, Kıtada C, Onda H, Kurokawa T, Nıshımura O, Fujıno M. 2001. Metastin suppresses the motility and growth of CHO cells transfected with its receptor. Biochem Biophys Res Commun 286: 958–963
26. Kadokawa H, Matsuı M, Hayashı K, Matsunaga N, Kawashıma C, Shımızu T, Kıda K, Mıyamoto A. 2008. Peripheral administration of kisspeptin-10 increases plasma concentrations of growth hormone as well as luteinizing hormone in prepubertal Holstein heifers. J Endocrinol 196: 331–334.
27. Kauffman AS, Clıfton DK, Steıner RA. 2007. Emerging ideas about kisspeptin- GPR54 signaling the neuroendocrine regulation of reproduction. Trends Neurosci. 30(10): 5045
28. Kınoshıta, M Tsukamura, H Adachı, S Matsuı, H Uenoyama, Y Iwata, K. (2005). Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology 146: 4431–6.
29. Kirby HR, Maguıre JJ, Colledge WH, Davenport AP. 2010. International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function. Pharmacol Rev. 62(4): 565-578.
30. Lee JH, Mıele ME, Hıcks DJ, Phıllıps KK, Trent JM, Weıssman BE, Welch D.R. 19 KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88: 1731 – 1737
31. Lehman MN, Merkley CM, Coolen LM, Goodman RL. 2010. Anatomy of the kisspeptin neural network in mammals. Brain Res.1364: 90-102.
32. Magee C, Foradorı CD, Bruemmer JE, Arreguın-Arevalo JA, Mccue PM, Handa RJ, Squıres EL, Clay CM. 2009. Biological and anatomical evidence for kisspeptin regulation of the hypothalamic-pituitarygonadal axis of estrous horse mares. Endocrinology. 150(6): 2813-21.
33. Makri A, Pıssımıssıs N, Lembessıs P, Polychronakos C, Koutsılıerıs M. 2008. The kisspeptin (KiSS-1)/GPR54 system in cancer biology. Cancer Treat Rev. 34(8): 682
34. Mead EJ, Maguıre JJ, Kuc RE, Davenport AP. 200 Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor GPR54, to atherosclerosis prone vessels. Endocrinology 148(1):140–147 Meczekalski B, Podfıgurna-Stopa A, Genazzanı AR. 2011. Why kisspeptin is such important for reproduction? Gynecol Endocrinol. 27(1):8-13.
35. Messager S, Chatzıdakı EE, Ma D, Hendrıck AG, Zahn D, Dıxon, J Thresher, R.R Malınge, I Lomet, D Carlton, M.B Colledge, W.H Caraty, A Aparıcıo, S.A. 200 Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA. 102(5):1761-1766.
36. Mikkelsen JD, Bentsen AH, Ansel L, Sımonneaux V, Juul A. 2009. Comparison of the effects of peripherally administered kisspeptins. Regul Pept. 152: 95–100
37. Millar RP, Roseweır AK, Tello JA, Anderson RA, George JT, Morgan K, Pawson AJ. 2010. Kisspeptin antagonists: Unraveling the role of kisspeptin in reproductive physiology Brain Res. 1364: 81-89, Ohtaki T, Shıntanı Y, Honda S, Matsumoto H, Horı A, Kanehashı K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishıbashı Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kıtada C, Usukı S, Kurokawa T, Onda H, Nıshımura O, Fujıno M. 2001. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411: 613–617
38. Okamura H, Yamamura T, Wakabayashi Y. 20 Kisspeptin as a master player in the central control of reproduction in mammals: An overview of kisspeptin research in domestic animals. Anim Sci J. 84: 369–381, Pompolo S, Pereıra A, Estrada KM, Clarke IJ. 200 Colocalization of kisspeptin and gonadotropin-releasing hormone in the ovine brain, Endocrinology 147: 804–810 Richard N, Corvaısıer S, Camacho E, Kottler ML. 2009. KiSS-1 and GPR54 at the pituitary level: overview and recent insights. Peptides. 30(1): 123-9.
39. Rişvanlı A, Apaydın AM, Bulut H, Tımurkaan N, Saat N. 2010. The effects of Kisspeptin antibodies on delayed estrus in rats. Gynecol Endocrinol. 26(4): 297-301.
40. Roa J, Aguılar E, Dıeguez C, Pınılla L, TenaSempere M. 2008. New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function. Front Neuroendocrinol 29: 48 – 69.
41. Roa J, Tena-Sempere M. 2007. KiSS-1 system and reproduction: comparative aspects and roles in the control of female gonadotropic axis in mammals. Gen Comp Endocrinol. 153(13):132-40
42. Roseweir AK, Mıllar RP. 2009. The role of kisspeptin in the control of gonadotrophin secretion. Hum Reprod Update. 15(2): 203-12 Sawyer I, Smıllıe SJ, Bodkın JV, Fernandes E, O'byrne KT, Braın SD. 2011. The Vasoactive Potential of Kisspeptin-10 in the Peripheral Vasculature. PLoS One 6(2): e146
43. Silvestre RA, Egıdo EM, Hernandez R, Marco J. 200 Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas. J Endocrinol. 196(2):283-90 Smith JT, Clay CM, Caraty A, Clarke IJ. 2007. KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season Endocrinology.148(3):1150-7
44. Smith JT. 2008. Kisspeptin signalling in the brain: Steroid regulation in the rodent and ewe. Brain Res Rev. 57(2):288-98
45. Smith JT, Rao A, Pereıra A, Caraty A, Mıllar RP, Clarke IJ. 2008a. Kisspeptin is present in ovine hypophysial portal blood but does not increase during the preovulatory luteinizing hormone surge: evidence that gonadotropes are not direct targets of kisspeptin in vivo. Endocrinology. 149(4):1951-9
46. Smith JT, Coolen L, Krıegsfeld L, Sarı I, Jaafarzadehshırazı M, Maltby M, Bateman K, Robert L, Goodman R, Tılbrook A, Ubuka T, Bentley G, Clarke I, Lehman M. 2008b. Variation in Kisspeptin and RFamideRelated Peptide (RFRP) Expression and Terminal Connections to GonadotropinReleasing Hormone Neurons in the Brain: A Novel Medium for Seasonal Breeding in the Sheep. Endocrinology 149: 5770-5782.
47. Smith JT. 2009. Sex steroid control of hypothalamic Kiss1 expression in sheep and rodents: comparative aspects. Peptides.30(1):94-102
48. Smith JT, Saleh SN, Clarke IJ. 2009a. Seasonal and cyclical change in the luteinizing hormone response to kisspeptin in the ewe, Neuroendocrinology 90: 283–29
49. Smith JT, Lı Q, Pereıra A, Clarke IJ. 2009b. Kisspeptin neurons in the ovine arcuate nucleus and preoptic area are involved in the preovulatory luteinizing hormone surge. Endocrinology. 150(12):5530-5538
50. Smith JT, Clarke IJ. 2010. Seasonal breeding as a neuroendocrine model for puberty in sheep. Mol Cell Endocrinol. 5,324(1-2):102-9.
51. Smith JT, Lı Q, Yap KS, Shahab M, Roseweır AK, Mıllar RP, Clarke I.J. 2011. Kisspeptin is essential for the full preovulatory LH surge and stimulates GnRH release from the isolated ovine median eminence. Endocrinology. 152(3):1001-1012.
52. Tena-Sempere M. 2010. Kisspeptin signaling in the brain: recent developments and future challenges. Mol Cell Endocrinol. 314(2):1641
53. Thompson EL, Amber V, Stamp GW, Patterson M, Curtıs AE, Cooke JH, Appleby GF, Dhıllo WS, Ghateı MA, Bloom SR, Murphy KG. 2009. Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms. Br J Pharmacol.156(4): 609-25.
54. Torricelli M, Gallerı L, Voltolını C, Bılıottı G, Florıo P, De Bonıs M, Petraglıa F. 2008. Changes of placental Kiss-1 mRNA expression and maternal/cord kisspeptin levels at preterm delivery. Reprod Sci. 15(8):779-84.
55. Wagner GC, Johnston JD, Clarke IJ, Lıncoln GA, Hazlerıgg DG. 2008. Redefining the limits of day length responsiveness in a seasonal mammal. Endocrinology 149: 32–9.