Please wait a minute...
Journal of ZheJiang University(Medical Science)  2017, Vol. 46 Issue (3): 328-333    DOI: 10.3785/j.issn.1008-9292.2017.06.17
    
Potential clinical application of Kisspeptin in reproductive endocrinology
FU Yanling, ZHU Yimin
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
Download:   PDF(979KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Gonadotropin-releasing hormone (GnRH) plays an important role in the process of reproduction. Studies have shown that a family of peptides Kisspeptin can act on GnRH-related neurons, stimulating the secretion of GnRH, and activating the hypothalamic-pituitary-gonadal axis. Both animal experiments and clinical studies have shown that exogenous administration of Kisspeptin is able to induce physiological GnRH release in healthy individuals and those with endocrine-disorders, which brings great hope for treatment of reproductive endocrine diseases. The effect of Kisspeptin is similar to the physiological process in induction of ovulation and ovum maturation, leading to high security and efficiency for women receiving in vitro fertilization. Kisspeptin is involved in trophoblast invasion, so it may be useful for predicting pregnancy outcomes. In addition, Kisspeptin is the key hormone in the onset of puberty acting as a signal transducer in metabolism and reproduction, so it provides some directions for studies of polycystic ovary syndrome, hyperprolactinemia, and other metabolic-related reproductive endocrine diseases. This article reviews the character of Kisspeptin and the prospect of its application in treatment of reproductive endocrine diseases.



Key wordsPeptide hormones/pharmacology      Gonadotropin-releasing hormone/secretion      Reproduction      Endocrine system diseases      Fertilization in vitro      Review     
Received: 01 June 2017      Published: 25 June 2017
CLC:  R714  
Cite this article:

FU Yanling, ZHU Yimin. Potential clinical application of Kisspeptin in reproductive endocrinology. Journal of ZheJiang University(Medical Science), 2017, 46(3): 328-333.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2017.06.17     OR     http://www.zjujournals.com/xueshu/med/Y2017/V46/I3/328


肽类激素Kisspeptin在生殖内分泌领域的应用前景

肽类激素Kisspeptin是调控女性生殖内分泌功能的重要激素,能作用于促性腺激素释放激素(GnRH)神经元,刺激GnRH分泌,从而激活下丘脑-垂体-性腺轴。在大量动物实验的基础上,越来越多的人体临床实验结果表明,外源性地给予Kisspeptin能够使健康个体甚至生殖内分泌紊乱的个体诱发生理性GnRH释放。Kisspeptin在诱导女性排卵及卵子成熟方面可能较传统药物更贴近生理过程,更具安全性和高效性,在体外受精治疗中有一定程度的优势。同时,Kisspeptin因其与滋养细胞浸润相关,可能用于预测妊娠结局。另外,Kisspeptin是启动青春期的关键激素,在人体代谢和生殖功能方面起到了信号传导作用,这为多囊卵巢综合征、高泌乳素血症等相关生殖内分泌疾病的诊治提示了新的研究思路。本文综述Kisspeptin在生殖内分泌领域的应用前景。


关键词: 肽类激素/药理学,  促性腺素释放激素/分泌,  生殖,  内分泌系统疾病,  受精,  体外,  综述 

[1] LEE J H, MIELE M E, HICKSD J, et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene[J]. J Natl Cancer Inst,1996,88(23):1731-1737.
[2] DE ROUX N, GENIN E, CAREL J C, et al. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54[J]. Proc Natl Acad Sci U S A,2003,100(19):10972-10976.
[3] SEMINARA S B, MESSAGER S, CHATZIDAKI E E, et al. The GPR54 gene as a regulator of puberty[J]. N Engl J Med,2003,349(17):1614-1627.
[4] SMITH J T, CUNNINGHAM M J, RISSMAN E F, et al. Regulation of Kiss1 gene expression in the brain of the female mouse[J]. Endocrinology,2005,146(9):3686-3692.
[5] GOTTSCH M L, CUNNINGHAM M J, SMITH J T, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse[J]. Endocrinology,2004,145(9):4073-4077.
[6] MATSUI H, TAKATSU Y, KUMANO S, et al. Peripheral administration of metasin induces marked gonadotropin release and ovulation in the rat[J]. Biochem Biophys Res Commun,2004,320(2):383-388.
[7] JAYASENA C N, ABBARA A, COMNINOS A N, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization[J]. J Clin Invest,2014,124(8):3667-3677.
[8] ABBARA A, JAYASENA C N, CHRISTOPOULOS G, et al. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy[J]. J Clin Endocrinol Metab,2015,100(9):3322-3331.
[9] BILBAN M, GHAFFARI-TABRIZI N, HINTERMANN E, et al. Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts[J]. J Cell Sci,2004,117(Pt 8):1319-1328.
[10] JAYASENA C N, ABBARA A, IZZI-ENGBEAYA C, et al. Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage[J]. J Clin Endocrinol Metab,2014,99(12):E2652-E2660.
[11] PARK D W, LEE S K, HONG S R, et al. Expression of Kisspeptin and its receptor GPR54 in the first trimester trophoblast of women with recurrent pregnancy loss[J]. Am J Reprod Immunol,2012,67(2):132-139.
[12] WU S, ZHANG H, TIANJ, et al. Expression of kisspeptin/GPR54 and PIBF/PR in the first trimester trophoblast and decidua of women with recurrent spontaneous abortion[J]. Pathol Res Pract,2014,210(1):47-54.
[13] PENG J, TANG M, ZHANG B P, et al. Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signaling pathway in rat luteal cells[J]. Fertil Steril,2013,99(5):1436-1443.e1.
[14] 吴邵花.Kisspeptin/GPR54表达异常与不明原因复发性流产发病关系的研究[D].苏州:苏州大学,2013. WU Shaohua. Study on relationship between dysfunction of Kisspeptin/GPR54 and the pathogenesis of unexplained recurrent spontaneous abortion[D]. Suzhou:Soochow University,2013. (in Chinese)
[15] CALDER M, CHAN Y M, RAJ R, et al. Implantation failure in female Kiss1-/-mice is independent of their hypogonadic state and can be partially rescued by leukemia inhibitory factor[J]. Endocrinology,2014,155(8):3065-3078.
[16] DHILLO W S, SAVAGE P, MURPHY K G, et al. Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment[J]. Am J Physiol Endocrinol Metab,2006,291(5):E878-E884.
[17] CETKOVI? A, MILJIC D, LJUBIC? A, et al. Plasma kisspeptin levels in pregnancies with diabetes and hypertensive disease as a potential marker of placental dysfunction and adverse perinatal outcome[J]. Endocr Res,2012,37(2):78-88.
[18] ARMSTRONG R A, REYNOLDS R M, LEASK R, et al. Decreased serum levels of kisspeptin in early pregnancy are associated with intra-uterine growth restriction and pre-eclampsia[J]. Prenat Diagn,2009,29(10):982-985.
[19] SÁNCHEZ-GARRIDO M A, RUIZ-PINO F, MANFREDI-LOZANOM, et al. Obesity-induced hypogonadism in the male:premature reproductive neuroendocrine senescence and contribution of Kiss1-mediated mechanisms[J]. Endocrinology,2014,155(3):1067-1079.
[20] PANIDIS D, ROUSSO D, KOLIAKOS G, et al. Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome[J]. Fertil Steril,2006,85(6):1778-1783.
[21] JEON Y E, LEE K E, JUNG J A, et al. Kisspeptin, leptin, and retinol-binding protein 4 in women with polycystic ovary syndrome[J]. Gynecol Obstet Invest,2013,75(4):268-274.
[22] EMEKCI O O, OZAY A C, ACARB, et al. Role of kisspeptin in polycystic ovary syndrome (PCOS)[J]. Gynecol Endocrinol,2016,32(9):718-722.
[23] VÁZQUEZ M J, ROMERO-RUIZ A, TENA-SEMPEREM. Roles of leptin in reproduction, pregnancy and polycystic ovary syndrome:consensus knowledge and recent developments[J]. Metabolism,2015,64(1):79-91.
[24] NAVARRO V M, CASTELLANO J M, FERNÁNDEZ-FERNÁNDEZ R, et al. Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide[J]. Endocrinology,2004,145(10):4565-4574.
[25] AKINCI A, CETIN D, ILHANN. Plasma kisspeptin levels in girls with premature thelarche[J]. J Clin Res Pediatr Endocrinol,2012,4(2):61-65.
[26] 熊翔宇,杨玉.血浆Kisspeptin水平对女童中枢性性早熟的诊断及疗效评估的意义[J].中华实用儿科临床杂志,2014,29(8):612-615. XIONG Xiangyu, YANG Yu. Significance of Kisspeptin levels in diagnosis and therapeutic evaluation of idiopathic central precocious puber in girls[J]. Journal of Applied Clinical Pediatrics,2014,29(8):612-615.
[27] OZTIN H, CAGILTAY E, CAGLAYAN S, et al. Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male patients and its relation with glucose-insulin dynamic[J]. Gynecol Endocrinol,2016,32:991-994.
[28] SONIGO C, BOUILLY J, CARRÉN, et al. Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration[J]. J Clin Invest,2012,122(10):3791-3795.
[29] BYRI P, GANGINENI A, REDDYK R, et al. Effect of kisspeptin on in vitro maturation of sheep oocytes[J]. Vet World,2017,10(3):276-280.

[1] XU Jingjing, TAN Yanbin, ZHANG Minming. Medical imaging in tumor precision medicine: opportunities and challenges[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 455-461.
[2] PAN Jingying, HE Mengye, KE Wei, HU Menglin, WANG Meifang, SHEN Peng. Advances on correlation of PET-CT findings with breast cancer molecular subtypes, treatment response and prognosis[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 473-480.
[3] ZHANG Siying, CHEN Feng. Research progress of CT/MRI parametric response map in precision evaluation of therapeutic response of cancer patients[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 468-472.
[4] PAN Yao, CHEN Jieyu, YU Risheng. Accurate imaging diagnosis and evaluation of pancreatic cancer[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 462-467.
[5] WANG Mengyan, ZHU Biao. Research progress on genes mutations related to sulfa drug resistance in Pneumocystis jirovecii[J]. Journal of ZheJiang University(Medical Science), 2017, 46(5): 563-569.
[6] LI Yandie, LU Meiping. Progress on the study of NLRP3 inflammasome in autoinflammatory diseases of children[J]. Journal of ZheJiang University(Medical Science), 2017, 46(4): 449-453.
[7] WANG Liya, QIAN Yeqing, JIN Fan. Research progress on the safety of offsprings conceived by assisted reproductive technology[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 279-284.
[8] LI Enshu, YE Xiaoqun, FANG Li, YE Yinghui. Effect of oxygen concentration on outcome of in-vitro fertilization-embryo transfer[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 290-294.
[9] YAN Kai, JIN Fan. Advances on prenatal diagnosis of birth defects associated with genetic disorders[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 227-232.
[10] HU Xiaorui, MO Fengyi, MA Qing, CUI Long, LYU Pingping, YE Yinghui. Correlation of fetuin-B concentrations in serum and follicular fluid with outcomes of in vitro fertilization[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 285-289.
[11] TANG Minyue, ZHU Yimin. The involvement of galectin-1 in implantation and pregnancy maintenance at the maternal-fetal interface[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 321-327.
[12] SHI Biwei, CUI Long, YE Xiaoqun, YE Yinghui. Effects of embryo cryopreservation and thawing on clinical outcomes of transplantable embryos after cleavage-stage preimplantation genetic diagnosis or screening[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 295-299.
[13] FU Xiaohua, XU Weihai, QIU Shengchun, SHU Jing. Research progress on the relationship of brown adipose tissue with polycystic ovary syndrome[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 315-320.
[14] QIAN Yeqing, WANG Liya, LUO Yuqin, YAN Kai, DONG Minyue, JIN Fan. Advances in the application of high-throughput sequencing in clinical genetics[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 334-337.
[15] SHEN Dan, WANG Fangfang, JIANG Zhou, QU Fan. Long-term effects of polycystic ovary syndrome on the offspring[J]. Journal of ZheJiang University(Medical Science), 2017, 46(3): 300-304.