王 濱 柳學周 徐永江 史 寶 劉 權

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Kisspeptin對魚類生殖軸的調控機制研究*

王 濱1,2#柳學周1,2,①#徐永江1,2史 寶1,2劉 權1,3

(1. 農業(yè)農村部海洋漁業(yè)可持續(xù)發(fā)展重點實驗室 中國水產科學研究院黃海水產研究所 青島 266071； 2. 青島海洋科學與技術試點國家實驗室海洋漁業(yè)科學與食物產出過程功能實驗室 青島 266071； 3. 上海海洋大學水產與生命學院 上海 201306)

Kisspeptin (簡稱Kiss或者Kp)是由基因編碼的一種下丘腦神經(jīng)肽，通過其受體KissR(也稱作GPR54)的介導參與了多種生理過程，如抑制腫瘤轉移和參與生殖調控。目前，盡管在鯉形目(Cypriniformes)、鱸形目(Perciforms)、鰈形目(Pleuronectiforms)、鲀形目(Tetraodontiforms)、頜針目(Beloniforms)、鲉形目(Scorpaeniformes)、鮭形目(Salmoniformes)及鱈形目(Gadiformes)等多種魚類中均鑒定出了基因，但Kiss/KissR系統(tǒng)在魚類生殖調控中的精確作用及其分子機制尚未完全闡明。尤其是在魚類中存在2種及3種基因，Kiss/KissR系統(tǒng)對魚類生殖調控的作用方式更加復雜。本文簡要總結魚類Kiss及其受體的研究進展，并對Kiss的生理學功能、信號轉導機制以及表達調控研究進行概括討論，旨在加深對魚類Kiss/KissR系統(tǒng)的認識和了解，為后續(xù)研究指明方向。

魚類；Kisspeptin；kisspeptin receptor；生殖；信號轉導；基因表達調控

下丘腦神經(jīng)肽kisspeptin及其受體KissR在哺乳動物生殖調控及青春期啟動中發(fā)揮了重要作用(Roa, 2011; Tena-Sempere, 2010)。迄今，除鳥類外，在其他脊椎動物中均鑒定出了基因。除鴨嘴獸()外，哺乳類只存在基因；兩棲類存在及三種基因；爬行類只存在基因；斑馬魚()、青鳉()、金魚()、歐洲海鱸()、條紋鱸()及鮐魚()中存在和兩種基因。相反，在尼羅羅非魚()、斜帶石斑魚()、塞內加爾鰨()、半滑舌鰨()以及星點東方鲀()中只鑒定出了基因(Pasquier, 2014; Um, 2010; Wang, 2017b)。目前，已在多種魚類中鑒定出了Kiss系統(tǒng)，其在魚類生殖調控中的生理功能研究也日益完善(Akazome, 2010; Mechaly, 2013; Tena- Sempere, 2012)。本文簡要總結魚類Kiss及其受體的研究進展，并對Kiss的生理學功能、信號轉導機制以及表達調控研究進行概括討論，旨在加深對魚類Kiss/KissR系統(tǒng)的認識和了解，為后續(xù)研究奠定基礎。

1 Kisspeptin的發(fā)現(xiàn)及與生殖的關系

基因最初是從人()黑色素瘤和乳腺癌細胞中分離得到的，因其具有抑制腫瘤生長和轉移的功能，Kiss最初被命名為轉移抑制素(Metastin) (Lee, 1996、1997)。Lee等(1999)從大鼠()腦中鑒定出了1種新型G蛋白偶聯(lián)受體，命名為GPR54。2年后，Kiss被認為是孤兒受體GPR54的內源性配體(Kotani, 2001; Muir, 2001; Ohtaki, 2001)。2003年，2個獨立研究組發(fā)現(xiàn)，突變導致人特發(fā)性性腺功能減退(de Roux, 2003; Seminara, 2003)。隨后研究發(fā)現(xiàn)，基因敲除或者均影響性腺發(fā)育及生殖功能(d￠Anglemont de Tassigny, 2007; Seminara, 2003)，說明Kiss/GPR54系統(tǒng)在哺乳類生殖調控中發(fā)揮了關鍵作用。

近幾年，kisspeptin在魚類生殖調控中的作用也有較多研究。如Kiss1直接促進了金魚垂體細胞黃體生成素(Luteinizing hormone, LH)分泌(Chang, 2012; Yang, 2010)。Kiss2也促進了歐洲海鱸(Espigares, 2015b)和條紋鱸(Zmora, 2015)垂體細胞LH及卵泡刺激素(Follicle-stimulating hormone, FSH)分泌。此外，Kiss1增加了金魚垂體細胞的表達水平(Yang, 2010)。然而，Kiss1特異性地降低了歐洲鰻鱺垂體細胞的表達水平 (Pasquier, 2011)。腹腔注射Kiss2促進了斑馬魚垂體及的表達水平(Kitahashi, 2009)，而Kiss2特異性地促進了斜帶石斑魚垂體的表達量，對的表達水平無影響(Shi, 2010)。綜上所述，kisspeptin參與了魚類生殖調控，但具體作用機制因物種而異。

2 魚類kiss基因類型、結構及時空表達特性

由于基因不是很保守，直到2008年才在非哺乳類中鑒定出了其同源基因。van Aerle等(2008)利用全基因組序列及比較共線性方法，首次在斑馬魚和青鳉等5種魚類中鑒定出了基因。隨后，Biran等(2008)和Kanda等(2008)也通過類似方法，分別在斑馬魚和青鳉中獲得了基因。2009年，基因首次在斑馬魚、青鳉和歐洲海鱸中被鑒定出來(Felip, 2009; Kitahashi, 2009)。斑馬魚基因編碼116個氨基酸的前體多肽，其C末端核心十肽為YNLNSFGLRY (Y-Y形式) (Biran, 2008; van Aerle, 2008)；斑馬魚基因編碼125個氨基酸的前體多肽，其C末端核心十肽為FNYNPFGLRF (F-F形式) (Kitahashi, 2009)。與之類似，其他魚類C末端十肽序列與斑馬魚高度保守，該十肽也是發(fā)揮其功能所需的最短序列(Akazome, 2010; Pasquier, 2014)。在哺乳類中，基因由3個外顯子和2個內含子組成，其中，外顯子1只編碼一部分5￠UTR，外顯子2編碼另一部分5￠UTR及一部分CDS，剩余另一部分CDS及3￠UTR由外顯子3編碼(Pasquier, 2014)。同樣，斑馬魚基因也是由3個外顯子和2個內含子組成，而基因由2個外顯子和1個內含子組成(Kitahashi, 2009)。塞內加爾鰨基因也是由2個外顯子和1個內含子組成，但是，其存在2種剪接變異體：較短亞型編碼正常Kiss2前體多肽；較長亞型編碼一種縮短形式的無功能多肽(Mechaly, 2011)。

魚類及的組織分布因物種而異，即使同一物種不同腦區(qū)表達也有所差異。斑馬魚主要在間腦和中腦中表達，其次為后腦，在端腦和垂體中表達量較低(Biran, 2008)；在外周組織中，斑馬魚在胰腺和前腸中表達量較高，其次為性腺(Biran, 2008)。與之類似，青鳉(Felip, 2009; Kitahashi, 2009)、歐洲海鱸(Felip, 2009)、金魚(Li, 2009; Yang, 2010)、鮐魚(Shahjahan, 2010)等腦和性腺中表達量也較高。也主要在腦和性腺中高表達，如斑馬魚(Kitahashi, 2009)、青鳉(Kitahashi, 2009)、金魚(Li, 2009)、歐洲海鱸(Felip, 2009)、塞內加爾鰨(Mechaly, 2011)及南亞黑鯪() (Saha, 2016)等。此外，也在腸、腎臟、心臟等其他外周組織有所表達，具體表達模式具有物種特異性。

魚類基因在不同發(fā)育階段/生殖周期的表達模式也在斑馬魚等幾種魚類中有所報道。雌性斑馬魚腦表達量在孵化后逐漸升高，84 d時達到峰值；而雄性斑馬魚腦表達量在孵化后6周達到峰值，12周時有所下降(Biran, 2008)。此外，斑馬魚表達量在孵化后30 d達到峰值(Kitahashi, 2009)。上述結果顯示，可能參與了斑馬魚青春期啟動。鮐魚腦在不同生殖周期的表達模式具有性別二態(tài)性，雄性腦表達量隨精巢發(fā)育逐漸降低，而雌性腦表達量在卵巢發(fā)育過程中保持不變；除了分別在卵黃生成早期和精子生成晚期略微增加外，雌雄腦表達量隨性腺發(fā)育逐漸降低，均在產卵/排精后達到最小值(Selvaraj, 2010)。然而，精巢表達水平隨性腺發(fā)育逐漸升高，在精子成熟時期達到峰值；卵巢表達水平也隨性腺發(fā)育逐漸升高，在卵黃生成后期達到峰值(Selvaraj, 2010)。以上結果表明，可能參與了鮐魚季節(jié)性性腺發(fā)育。其他魚類表達水平也隨性腺發(fā)育而發(fā)生波動(Alvarado, 2013; Migaud, 2012; Park, 2016; Saha, 2016; Shahi, 2017)。

3 魚類kissr基因類型、結構及時空表達特性

通常，哺乳類下丘腦的表達水平在青春期顯著性增加(Dungan, 2006)。魚類的表達模式也與生殖周期有關。鯔魚腦的表達水平隨性腺發(fā)育而降低，在青春期前期表達量最高(Nocillado, 2007)。與之類似，軍曹魚、黑頭呆魚及大西洋庸鰈腦的表達量也均在青春期達到峰值(Filby, 2008; Mechaly, 2010; Mohamed, 2007)。斑馬魚腦的表達量在孵化后8周時顯著性增加，隨后回到本底水平；而的表達量在孵化后6周時顯著增加，隨后一直保持到12周(Biran, 2008)。鮐魚腦在不同生殖周期的表達模式具有性別二態(tài)性，雄魚腦及的表達水平不隨精巢發(fā)育過程而變化；而雌魚腦及的表達水平均在卵黃生成早期顯著增加并達到峰值，繼而隨卵巢發(fā)育過程又回到本底水平(Ohga, 2013)。精巢表達水平隨性腺發(fā)育逐漸升高，在精子成熟時期達到峰值；而精巢表達水平不隨性腺發(fā)育過程而變化(Ohga, 2013)。綜上所述，可能參與了魚類青春期啟動及季節(jié)性性腺發(fā)育。

4 Kisspeptin對魚類生殖調控作用研究

4.1 Kisspeptin對下丘腦促性腺激素釋放激素(Gonadotropin-releasing hormone, GnRH)神經(jīng)元活性以及表達調控的影響

GnRH是垂體促性腺激素合成與分泌的主要促進因子，在每種硬骨魚類中存在至少2種GnRH多肽(Zohar, 2010; 王濱等, 2017)。Parhar等(2004)首次在羅非魚中鑒定出了基因，并進一步證實在GnRH1、GnRH2及GnRH3神經(jīng)元中表達，這表明Kiss2能夠直接作用于GnRH神經(jīng)元，進而影響其活性及表達調控。在青鳉中，通過電生理學研究表明，Kiss1能夠促進GnRH3神經(jīng)元的電活動(Electrical activity)，而河豚毒素或者阻斷突觸傳遞均降低了Kiss1誘導的GnRH3神經(jīng)元的電活動，這表明Kiss1以間接方式通過突觸調控進而激活GnRH3神經(jīng)元的電活動(Zhao, 2012)。

4.2 Kisspeptin對垂體激素合成與分泌的影響

由于魚類中存在2種Kiss多肽，Kiss對魚類垂體激素分泌的影響更加復雜。肌肉注射Kiss1和Kiss2均提高了青春期前的歐洲海鱸血清LH水平(Felip, 2009)；腹腔注射Kiss1而非Kiss2也提高了性成熟雌性金魚血清LH水平 (Li, 2009)。但Kiss1和Kiss2均不影響金魚垂體細胞LH分泌(Li, 2009)。相反，另有研究表明，Kiss1直接促進了金魚垂體細胞LH分泌(Chang, 2012; Yang, 2010)。最近研究報道，Kiss2而非Kiss1促進了歐洲海鱸(Espigares, 2015b)和條紋鱸(Zmora, 2015)垂體細胞LH分泌。Kiss1和Kiss2對雜交條紋鱸LH分泌的調控作用與生殖周期相關。在青春前期，肌肉注射Kiss2而非Kiss1增加了血清中LH水平；在性腺復蘇期，Kiss1和Kiss2均增加了血清中LH水平(Zmora, 2012)。關于FSH分泌調控，肌肉注射Kiss2提高了青春期前的歐洲海鱸血清FSH水平，但是，Kiss1無影響(Felip, 2009)。同樣，Kiss2而非Kiss1促進了歐洲海鱸垂體細胞FSH分泌(Espigares, 2015b)。此外，Kiss1和Kiss2均促進了條紋鱸垂體細胞FSH分泌(Zmora, 2015)。而長期埋植Kiss2顯著性地降低了條紋鱸血清FSH水平(Zmora, 2014)。在魚類中，關于Kiss對GH分泌的影響僅見于金魚，Kiss1促進了金魚垂體細胞GH分泌(Chang, 2012; Yang, 2010)。綜上所述，Kiss對垂體激素分泌的調控作用因物種、生殖周期和注射途徑而異，甚至在同一物種的不同生殖周期Kiss1和Kiss2可能發(fā)揮了不同的作用。

4.3 Kisspeptin對性腺發(fā)育及類固醇激素分泌的影響

5 魚類kisspeptin的信號轉導機制

在哺乳類中，Kiss能夠激活多種細胞內信號通路，例如PLC/IP3/PKC、MAPK以及Ca2+通路等(Castano, 2009; Pasquier, 2014)，而非哺乳類中有關Kiss信號轉導機制的研究相對較少。在兩棲類中，Moon等(2009)通過CRE-luc(對應AC/PKA通路)和SRE-luc(對應PLC/PKC通路)報告系統(tǒng)表明，Kiss能夠激活轉染了牛蛙() Kiss2R的非洲綠猴腎纖維細胞系(CV-1 cells)中SRE-luc的活性，但對CRE-luc活性無影響。此外，PKC抑制劑GF109203X預處理CV-1細胞系顯著性地降低了Kiss誘導的SRE-luc的活性，而Rho激酶抑制劑Y-27632預處理CV-1細胞系部分阻斷了Kiss誘導的SRE-luc的活性，上述結果顯示，牛蛙Kiss2R可能主要與PKC通路偶聯(lián)，部分與Rho激酶通路偶聯(lián)(Moon, 2009)。同樣，非洲爪蟾() 3種KissR也都與PKC通路偶聯(lián)(Lee, 2009)。

6 魚類kiss/kissr系統(tǒng)的表達調控研究

6.1 性類固醇激素及甲狀腺激素對kiss/kissr系統(tǒng)的調控作用

Kiss/KissR系統(tǒng)也介導了睪酮(Testosterone, T)對生殖軸的反饋調控。一方面，用睪酮處理卵巢切除后的雌性條紋鱸，降低了其腦中、及的表達水平(Klenke, 2011)。另一方面，用睪酮處理精巢切除后的雄性歐洲海鱸，降低了其下丘腦中的表達水平，卻不影響、及的表達水平(Alvarado, 2016)。然而，睪酮促進了雄性歐洲海鱸垂體細胞及的表達水平，對的表達水平無影響(Espigares, 2015b)。此外，睪酮也不影響半滑舌鰨下丘腦中及的表達水平(Wang, 2017b)。目前，關于甲狀腺激素(Thyroid hormone)對魚類系統(tǒng)的調控作用僅見于羅非魚。腹腔注射甲狀腺激素，顯著地增加了羅非魚腦的表達水平，但由于甲狀腺激素受體不在Kiss2神經(jīng)元中表達，這表明甲狀腺激素是以間接的方式影響的表達(Ogawa, 2013)。綜上所述，性類固醇激素及甲狀腺激素通過影響系統(tǒng)的表達水平進而影響魚類生殖調控。

6.2 Kisspeptin等神經(jīng)肽對kiss/kissr系統(tǒng)的調控作用

促性腺激素抑制激素(Gonadotropin-inhibitory hormone, GnIH)是迄今為止在脊椎動物中鑒定出的唯一具有抑制生殖功能的下丘腦神經(jīng)肽，通過其受體GnIHR (之前被稱作GPR147)介導作用于腦-垂體-性腺軸進而影響動物生殖調控(Tsutsui, 2010; Ubuka, 2016; Wang, 2018)。目前，從魚類到哺乳類都鑒定出了的同源基因，并且每種魚類基因編碼有2種或者3種成熟多肽，即GnIH-1、GnIH-2及GnIH-3 (Ogawa, 2014; Tsutsui, 2010; Ubuka, 2016; 王濱等, 2016)。GnIH對的表達調控也有少數(shù)報道。在半滑舌鰨中，GnIH-1和GnIH-2均不影響下丘腦中的表達水平(劉權等, 2017)。腹腔注射斜帶石斑魚3種GnIH多肽也不影響其下丘腦的表達水平(Wang, 2015)。此外，哺乳類GnIH同源多肽RFRP3也不影響大鼠表達水平(Johnson, 2008)。盡管側腦室注射歐洲海鱸GnIH-1不影響其腦、及的表達水平，但是，GnIH-2均降低了及的表達水平，這說明在歐洲海鱸中，GnIH-2主要發(fā)揮了生殖調控的抑制作用(Paullada-Salmeron, 2016)。

6.3 光照對kiss/kissr系統(tǒng)的調控作用

光照是影響魚類及其他脊椎動物生殖調控的一個重要環(huán)境因子，其作用主要由松果體夜間分泌的褪黑激素介導(Kitahashi, 2013)。目前，關于光照對魚類系統(tǒng)的表達調控研究相對較少且存在爭議。如持續(xù)性光照降低了羅非魚腦的表達水平，表明光照能夠以直接或者間接的方式影響的表達(Martinez-Chavez, 2008)。同樣，持續(xù)性光照導致歐洲海鱸前中腦及的表達量不再隨季節(jié)變化而變化(Espigares, 2017)。長光照(繁殖狀態(tài))條件下，青鳉下丘腦核腹側結節(jié)中Kiss1神經(jīng)元的數(shù)量顯著性高于短光照(非繁殖狀態(tài)) (Kanda, 2008)。而在模擬自然光照(促進生殖)條件和持續(xù)性光照(抑制生殖)條件下，大西洋鱈()腦及的表達量無顯著性差異，這說明光照不影響大西洋鱈基因表達(Cowan, 2012)。特別是褪黑激素促進了斑馬魚腦及的表達水平(Carnevali, 2011)，卻抑制了歐洲海鱸腦及的表達水平(Alvarado, 2015)。綜上所示，Kiss/KissR系統(tǒng)可能介導了光照(及褪黑激素)對魚類生殖調控過程，然而具體作用機制因物種而異，需要進一步深入研究。

6.4 溫度對kiss/kissr系統(tǒng)的調控作用

對變溫動物而言，溫度是影響其生殖調控的一個重要環(huán)境因子。水溫升高或者降低均能抑制魚類生殖，但其分子機制仍不清楚。Kiss作為魚類生殖調控的一個重要因子，溫度對基因的表達調控作用也有了初步研究。斑馬魚最適繁殖溫度為26℃~ 28℃，低于20℃或者高于30℃均能降低其繁殖能力(Shahjahan, 2013)。將斑馬魚置于低溫(15℃)、正常溫度(27℃)和高溫(35℃) 7 d后研究發(fā)現(xiàn)，低溫組斑馬魚全腦的表達量顯著性增加，高溫組的表達量與正常組相比無顯著性差異；而低溫組和高溫組斑馬魚全腦的表達量較正常組均顯著性降低(Shahjahan, 2013)。此外，低溫也增加了斑馬魚松果體等部分腦區(qū)的表達量，然而，低溫和高溫均降低了斑馬魚下丘腦等部分腦區(qū)的表達量(Shahjahan, 2013)。上述結果表明，溫度調控斑馬魚及表達的作用機制是不同的，低溫激活了系統(tǒng)，而低溫和高溫均抑制了系統(tǒng)，說明和系統(tǒng)可能參與了斑馬魚不同的生理功能(Shahjahan, 2013)。

同樣，將星點東方鲀置于低溫(14℃)、正常溫度(21℃)和高溫(28℃) 7 d后研究發(fā)現(xiàn)，低溫組和高溫組性腺指數(shù)GSI顯著性降低；低溫組和高溫組腦/表達量也顯著性降低；與此同時，低溫和高溫組均抑制了腦、垂體及的表達水平(Shahjahan, 2016)。上述結果表明，低溫和高溫組通過抑制系統(tǒng)，進而阻斷星點東方鲀生殖。銀漢魚()的性別決定、分化與溫度緊密相關，低溫(17℃~19℃)導致100%全雌，高溫(29℃)導致100%全雄，而24℃~25°℃導致雌雄比例各半(Tovar Bohorquez, 2017)。在高溫條件下，銀漢仔魚整個腦部的表達量在孵化后4周顯著性增加；而在低溫條件下，腦部的表達量在孵化后8周內保持不變，這表明Kiss2可能在雄性發(fā)育過程中性別決定階段發(fā)揮了重要作用(Tovar Bohorquez, 2017)。

6.5 饑餓對kiss/kissr系統(tǒng)的調控作用

營養(yǎng)狀況也會影響動物生殖活動。目前，關于Kiss介導的能量平衡與生殖之間關系的研究較少。在哺乳類中，饑餓導致小鼠()下丘腦及表達量降低(Luque, 2007)。同樣，饑餓也降低了大鼠下丘腦的表達量，卻增加了的表達量(Castellano, 2005)。在魚類中，饑餓15 d導致塞內加爾鰨體重減少，卻增加了下丘腦及的表達水平，但對胃中及的表達水平無影響(Mechaly, 2011)。同樣，饑餓也增加了歐洲海鱸下丘腦、、及的表達水平(Escobar, 2016)。綜上所述，饑餓對哺乳類和魚類系統(tǒng)的不同調控作用表明，該系統(tǒng)可能在哺乳類和魚類能量平衡過程中起著相反的作用。此外，Kiss/KissR系統(tǒng)是否參與了魚類攝食調控仍不得而知，需要進一步深入研究。

7 小結

Kiss是一種多功能的神經(jīng)肽，它在下丘腦-垂體-性腺軸多個水平參與了哺乳動物生殖調控。目前，盡管已在多種魚類中鑒定出了Kiss/KissR系統(tǒng)，但其在魚類生殖調控中的精確作用需要進一步研究；Kiss調控垂體激素分泌及其基因表達的信號轉導機制網(wǎng)絡需要進一步完善；Kiss是否參與魚類攝食調控及其作用機制尚未闡明；Kiss與其他因子(例如GnIH、GnRH等)之間如何互作，在生殖軸各個水平將多種信號整合進而調控生殖等生理過程仍不清楚，只有闡明上述機制才能更好地了解Kiss參與魚類生殖、生長及代謝的協(xié)調過程。該綜述總結了魚類Kiss及其受體的研究進展，并對Kiss的生理學功能、信號轉導機制以及表達調控研究進行概括討論，增加了人們對Kiss/KissR系統(tǒng)參與魚類生殖調控機制的認識，為后續(xù)研究提供參考。

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(編輯 陳嚴)

Regulatory Mechanisms of Kisspeptin on the Reproductive Axis in Fish

WANG Bin1,2, LIU Xuezhou1,2①, XU Yongjiang1,2, SHI Bao1,2, LIU Quan1,3

(1. Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071; 2 Laboratory for Marine Fisheries and Food Production Processes, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266071,; 3 College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306)

Kisspeptin (Kiss or Kp), a novel physiologically active peptide encoded by thegene, activates its cognate receptor KissR (also known as GPR54) in various target tissues to exert disparate functions, including inhibition of tumor metastasis and control of reproductive function. Thegene was originally isolated from human melanoma and breast cancer cells, and kisspeptin was initially called metastin in consideration of its suppressive effects on tumor growth and metastasis. With the exception of the platypus, a mammalian monotreme, which has two forms of kisspeptin genes (and), there is only one ligand,and its receptor,in placental mammals. However, this situation is different and even complex in non-mammalian species. Three/genes were described in amphibians, while searches in the chicken genome databases failed to identify these paralogous genes. To date, multiple forms of/genes have been identified in many teleosts, including Cypriniformes, Perciforms, Pleuronectiforms, Tetraodontiforms, Beloniforms, Scorpaeniformes, Salmoniformes and Gadiformes. A dual kisspeptin system,11and, have been detected in medaka, zebrafish, goldfish, chub mackerel, striped bass, and European sea bass, while onlywas identified in orange-spotted grouper, grass puffer,,,, and half-smooth tongue sole. In addition, the physiological relevance and functions of the Kiss/KissR system for the neuroendocrine regulation of reproduction remains to be established in fish. It should be noted that the mechanisms underlying the actions of Kiss on the hypothalamo-pituitary-gonadal (HPG) axis are still far from being fully understood. Given the multiple forms ofandgenes obtained in teleosts, the regulation of fish reproduction by the Kiss system is even complex. This review briefly summarized the progress of research on Kiss and its receptors, with special emphasis on the physiological functions of Kiss in fish, the signaling transduction pathways as well as the regulation ofgene expression. We hope that this review will contribute to future studies.

Fish; Kisspeptin; kisspeptin receptor; Reproduction; Signal transduction; Regulation of gene expression

LIU Xuezhou, E-mail: liuxz@ysfri.ac.cn

10.19663/j.issn2095-9869.20170424001

S917; Q575; Q492

A

2095-9869(2018)04-0173-12

* 中國水產科學研究院基本科研業(yè)務費(2017HY-XKQ01; 2017GH05; 2018GH17)、中國水產科學研究院黃海水產研究所基本科研業(yè)務費(20603022016018)、國家自然科學基金(31602133；31502145)、山東省自然科學基金(ZR2016CB02)和國家海水魚類產業(yè)技術體系(CARS-47)共同資助[This work was supported by Grants from the Central Public-Interest Scientific InstitutionBasal Research Fund, CAFS (2017HY-XKQ01; 2017GH05; 2018GH17), Special Scientific Research Funds for Central Non-Profit Institutes, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences (20603022016018), the National Natural Science Foundation of China (31602133; 31502145), the Natural Science Foundation of Shandong Province (ZR2016CB02), and China Agriculture Research System (CARS-47)]. 王 濱，E-mail: wangbin@ysfri.ac.cn；柳學周，E-mail: liuxz@ysfri.ac.cn

# 共同第一作者

柳學周，研究員，E-mail: liuxz@ysfri.ac.cn

2017-04-24,

2017-05-18

王濱, 柳學周, 徐永江, 史寶, 劉權. Kisspeptin對魚類生殖軸的調控機制研究. 漁業(yè)科學進展, 2018, 39(4): 173–184

Wang B, Liu XZ, Xu YJ, Shi B, Liu Q. Regulatory mechanisms of Kisspeptin on the reproductive axis in fish. Progress in Fishery Sciences, 2018, 39(4): 173–184