KISS-1/GPR54, KISS-1/GPR54 genes and their role in reproduction. FENG Tao 1, CHU Ming-Xing 2, ZHANG Ying-Jie 1 KISS-1/GPR54. GnRH( ) KISS-1 GPR54,
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1 HEREDITAS (Beijing) , 30(4): ISSN 综述 DOI: /SP.J KISS-1/GPR54 冯涛 1, 储明星 2, 张英杰 1 1., ; 2.,, : KISS-1 及其受体 GPR54 基因对青春期的正常启动具有重要作用 青春期开始前后, 动物下丘脑中 KISS-1 和 GPR54 mrna 水平很高, Kisspeptins(KISS-1 基因产物 ) 通过激活 GPR54 增加促性腺激素的释放, KISS-1 基因的表达受性腺类固醇激素的调控 GPR54 基因突变可以导致人和鼠的特发性促性腺激素分泌不足性腺机能减退症和促性腺激素依赖性性早熟 文章还介绍了 KISS-1 GPR54 基因的结构 表达 多态性以及和其它生殖调控因子之间的相互关系 : KISS-1 基因 ; GPR54 基因 ; Kisspeptin; 生殖 ; 调控 KISS-1/GPR54 genes and their role in reproduction FENG Tao 1, CHU Ming-Xing 2, ZHANG Ying-Jie 1 1. College of Animal Science and Technology, Gansu Agricultural University, Lanzhou , China; 2. The Key Laboratory of Domestic Animal Genetic Resources and Germplasm Innovation of CAAS, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing , China Abstract: KISS-1 gene and its receptor gene GPR54 play key roles in the initiation of puberty onset. The peptide product of the KiSS-1 gene, Kisspeptins stimulate gonadotrophins release to initiate puberty through the expression of GPR54 gene in the brain. So the level of KISS-1 and GPR54 mrna in hypothalamus was very high on the onset of puberty. The expression of KISS-1gene was regulated by steroid hormone in different nuclei within the forebrain to control the reproduction in puberty. Loss of function mutations of GPR54 gene could cause idiopathic hypogonadotropic hypogonadism (IHH) and gonadotrophin-dependant premature puberty. This review also introduced the structure, expression, homology comparison, polymorphism of KISS-1 and GPR54 genes and their interrelation with other regulators of reproduction. Keywords: KISS-1 gene; GPR54 gene; kisspeptin; reproduction; modulation,, GnRH( ), [1], KISS-1/GPR54,, KISS-1 GPR54,, (HPG) 收稿日期 : ; 修回日期 : 基金项目 : 973 (No.2006CB102105) 863 (No.2006AA10Z139) (No ) [Supported by National Key Basic Research and Development Program of China (No.2006CB102105), Hi-Tech Research and Development Program of China (No.2006AA10Z139), and National Natural Science Foundation of China (No )] 作者简介 : (1980 ),,,, : Tel: ; fengt@gsau.edu.cn 通讯作者 : (1968 ),,,,,, : Tel: ; mxchu@263.net
2 420 HEREDITAS (Beijing) KISS-1 GPR KISS-1 Lee [2] KISS-1 1q32-41, 4 3,, , [3,4] 2001, Kisspeptin, KISS-1 145, 19, 54, ( ), ( 121~124 ) Kisspeptin Kisspeptin-14, -13, -10 ( 1), Kisspeptins, Kisspeptin 54, metastin(, ) Kisspeptin-54 [1], Kisspeptin GPR54, Kisspeptins C -Arg-Phe-NH 2 (-Rfamide)( - ), [5], metastin 52 [1] [6] 1.2 GPR54 GPR54(G protein-coupled receptor 54) KISS-1, GPR54 KISS-1, G, Kisspeptin [7] 1999, GPR54 Lee [8] 2001, GPR54, 19, AXOR12 hot7t175, bp, 398, 7 3, 75 kda [9] Ishwar [10] GPR54 cdna,, 1 131, 377, GPR54 56% GPR54 cdna,, (GenBank NM_ AY NM_ NM_ DQ459345/ 46),, (GenBank XM_ AB_ ABC ), 80%, KISS-1 45%, 20% KISS-1/GPR54 [6] 2 KISS-1 GPR KISS-1 1 Kisspeptins [1] Fig. 1 Structural features of human Kisspeptins [1], KISS-1 cdna,, GenBank : NM_ XM_ AY XM_ DQ NM_ NM_178260, 85%, 45%~50% KISS-1 cdna KISS-1 GPR54 PCR(RT-PCR) (IR, immunohistochemistry reaction) KISS-1,, KISS-1 mrna, [1] KISS-1, [11,12], (ARC) (AVPV) [13] KISS-1, KISS-1 mrna, AVPV [7]
3 4 : KISS-1/GPR GPR54 GPR54,, [11,14] Kotani [15], GPR54, Felecia [9] KISS-1 GPR54, KISS-1/GPR54 [1], Kisspeptin [16] 3 KISS-1 GPR KISS-1/GPR54, KISS-1 GPR54 mrna [7],, KISS-1 GPR54 mrna [17] ;, KISS-1 mrna, GnRH GPR54, KISS-1 Kisspeptin [18] Kisspeptins, Kisspeptin-10 ; Kisspeptin-10 GnRH [1], GPR54 (idiopathic hypogonadotropic hypogonadism, IHH) KISS-1/GPR54, GPR54,,, ;, [14] GPR54 GnRH, KISS-1/GPR54 [20], Kisspeptin 90%, Kisspeptin [19] GPR54 IHH, GPR54 [20] Kisspeptin-10, 1 pmol (LH), ; Kisspeptin-10, GnRH LH, KISS-1/GPR54 [1] Kisspeptin : Kisspeptins ; Kisspeptins GnRH, GPR54 [7,21,23] 3.2 Kisspeptin Kisspeptins Gottsch [22], Kisspeptin-52 Kisspeptin-10, LH FSH, [1,23] [24] [21] [25], Kisspeptin,, [16] Kisspeptins GPR54 Kisspeptins GnRH [21,23,26] GnRH, GPR54 [15,27] Irwig [28] 77% GnRH GPR54, 55% 90%, Kisspeptin GnRH, Heather [7] Kisspeptins, GnRH, GPR54, GnRH GPR54, Kisspeptin, Kisspeptin [29] Kisspeptin-10 LH GPR54, GnRH, Kisspeptin GPR54 [1] (ICV)Kisspeptin-52 Kisspeptin-54
4 422 HEREDITAS (Beijing) GnRH, ICV Kisspeptin-10 GnRH [24] (OVX) ARC, KISS-1 Kisspeptin GnRH [30] Kisspeptin LH (FSH) (T) [31], Parhar [32] 45%~60% GnRH GPR54, Kisspeptin GnRH Kisspeptin GnRH [1] Kisspeptin Murphy [33] Kisspeptin HPG,, LH T, 13 T,, E ARC KISS-1 [16] KISS-1 Heather [7] KISS-1 ( 2) Kisspeptins, KISS-1 mrna ARC AVPV Kisspeptins GnRH, LH FSH, Kisspeptin, KISS-1 ARC, AVPV KISS-1 LH 3.3 KISS-1 KISS-1 ( ) KISS-1 KISS-1 mrna ARC, KISS-1, ; AVPV, KISS-1, KISS-1 LH [34] KISS-1 [16] Smith [30] OVX (E) (P) OVX, KISS-1 ARC E P, Kisspeptin GnRH KISS-1, KISS-1 ARC, GPR54 [21], GPR54 mrna, E P ARC KISS-1, 2 KISS-1 KISS-1 [7] Fig. 2 KISS-1 stimulates gonadotrophin secretion and gonadal steroids regulate KISS-1 expression [7] 3.4 KISS (Melatonin) Malpaux [35], KISS-1 (SD), ARC KISS-1, KISS-1 [36] KISS-1, (Leptin) Leptin, ARC, [37] Leptin [38], GnRH [39],
5 4 : KISS-1/GPR54 423, KISS-1 [40] ob/ob [41] ARC KISS-1 mrna, Leptin ARC KISS-1 mrna, 60% KISS-1 Leptin Kisspeptins Leptin KISS-1 [41] 3.4.3,, Greives [42] SD,, AVPV Kisspeptin, ARC Kisspeptin, AVPV Kisspeptin, ARC, Kisspeptin LH Kisspeptin,, KISS-1 [36,43] 3.4.4, [11] KISS-1 GPR54 mrna, LH Kisspeptin, GnRH Kisspeptin 60%, Kisspeptin [40] Kisspeptin, [31] ARC KISS-1 mrna [44] OVX ARC KISS-1 mrna [30], KISS-1 mrna [43] 4 GPR54 GPR54 IHH Semple [45] IHH,, C223R( 223 ) R297L( 297 ), GPR54, Kisspeptin GPR54 Lanfranco [46] PCR-SSCP IHH GPR54 R262Q IHH, GPR C,, 43,, LH FSH Tenenbaum-Rakover [47] IHH T305C, L102P( 102 ), GPR54 Felecia [9] IHH, GPR54 3 C T, (L148S); IHH 331 C T, (R331X, ), T A, (X399R, ), Felecia GPR54 ( 3), [9] IHH, Teles [48] GPR54 GnRH KISS-1 3 GPR54 [9] Fig. 3 Published coding sequence mutations of GPR54 and its coding sequence SNPs [9]
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