Kisspeptin對(duì)魚(yú)類生殖軸的調(diào)控機(jī)制研究*

王 濱 柳學(xué)周 徐永江 史 寶 劉 權(quán)

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Kisspeptin對(duì)魚(yú)類生殖軸的調(diào)控機(jī)制研究*

王 濱1,2#柳學(xué)周1,2,①#徐永江1,2史 寶1,2劉 權(quán)1,3

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Kisspeptin (簡(jiǎn)稱Kiss或者Kp)是由基因編碼的一種下丘腦神經(jīng)肽，通過(guò)其受體KissR(也稱作GPR54)的介導(dǎo)參與了多種生理過(guò)程，如抑制腫瘤轉(zhuǎn)移和參與生殖調(diào)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(yú)類中均鑒定出了基因，但Kiss/KissR系統(tǒng)在魚(yú)類生殖調(diào)控中的精確作用及其分子機(jī)制尚未完全闡明。尤其是在魚(yú)類中存在2種及3種基因，Kiss/KissR系統(tǒng)對(duì)魚(yú)類生殖調(diào)控的作用方式更加復(fù)雜。本文簡(jiǎn)要總結(jié)魚(yú)類Kiss及其受體的研究進(jìn)展，并對(duì)Kiss的生理學(xué)功能、信號(hào)轉(zhuǎn)導(dǎo)機(jī)制以及表達(dá)調(diào)控研究進(jìn)行概括討論，旨在加深對(duì)魚(yú)類Kiss/KissR系統(tǒng)的認(rèn)識(shí)和了解，為后續(xù)研究指明方向。

魚(yú)類；Kisspeptin；kisspeptin receptor；生殖；信號(hào)轉(zhuǎn)導(dǎo)；基因表達(dá)調(diào)控

下丘腦神經(jīng)肽kisspeptin及其受體KissR在哺乳動(dòng)物生殖調(diào)控及青春期啟動(dòng)中發(fā)揮了重要作用(Roa, 2011; Tena-Sempere, 2010)。迄今，除鳥(niǎo)類外，在其他脊椎動(dòng)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(yú)()、青鳉()、金魚(yú)()、歐洲海鱸()、條紋鱸()及鮐魚(yú)()中存在和兩種基因。相反，在尼羅羅非魚(yú)()、斜帶石斑魚(yú)()、塞內(nèi)加爾鰨()、半滑舌鰨()以及星點(diǎn)東方鲀()中只鑒定出了基因(Pasquier, 2014; Um, 2010; Wang, 2017b)。目前，已在多種魚(yú)類中鑒定出了Kiss系統(tǒng)，其在魚(yú)類生殖調(diào)控中的生理功能研究也日益完善(Akazome, 2010; Mechaly, 2013; Tena- Sempere, 2012)。本文簡(jiǎn)要總結(jié)魚(yú)類Kiss及其受體的研究進(jìn)展，并對(duì)Kiss的生理學(xué)功能、信號(hào)轉(zhuǎn)導(dǎo)機(jī)制以及表達(dá)調(diào)控研究進(jìn)行概括討論，旨在加深對(duì)魚(yú)類Kiss/KissR系統(tǒng)的認(rèn)識(shí)和了解，為后續(xù)研究奠定基礎(chǔ)。

1 Kisspeptin的發(fā)現(xiàn)及與生殖的關(guān)系

基因最初是從人()黑色素瘤和乳腺癌細(xì)胞中分離得到的，因其具有抑制腫瘤生長(zhǎng)和轉(zhuǎn)移的功能，Kiss最初被命名為轉(zhuǎn)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(rèn)為是孤兒受體GPR54的內(nèi)源性配體(Kotani, 2001; Muir, 2001; Ohtaki, 2001)。2003年，2個(gè)獨(dú)立研究組發(fā)現(xiàn)，突變導(dǎo)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(shuō)明Kiss/GPR54系統(tǒng)在哺乳類生殖調(diào)控中發(fā)揮了關(guān)鍵作用。

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

2 魚(yú)類kiss基因類型、結(jié)構(gòu)及時(shí)空表達(dá)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(yú)和青鳉等5種魚(yú)類中鑒定出了基因。隨后，Biran等(2008)和Kanda等(2008)也通過(guò)類似方法，分別在斑馬魚(yú)和青鳉中獲得了基因。2009年，基因首次在斑馬魚(yú)、青鳉和歐洲海鱸中被鑒定出來(lái)(Felip, 2009; Kitahashi, 2009)。斑馬魚(yú)基因編碼116個(gè)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(yú)基因編碼125個(gè)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(yú)類C末端十肽序列與斑馬魚(yú)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(gè)外顯子和2個(gè)內(nèi)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(yú)基因也是由3個(gè)外顯子和2個(gè)內(nèi)含子組成，而基因由2個(gè)外顯子和1個(gè)內(nèi)含子組成(Kitahashi, 2009)。塞內(nèi)加爾鰨基因也是由2個(gè)外顯子和1個(gè)內(nèi)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(zhǎng)亞型編碼一種縮短形式的無(wú)功能多肽(Mechaly, 2011)。

魚(yú)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(dá)也有所差異。斑馬魚(yú)主要在間腦和中腦中表達(dá)，其次為后腦，在端腦和垂體中表達(dá)量較低(Biran, 2008)；在外周組織中，斑馬魚(yú)在胰腺和前腸中表達(dá)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(yú)(Li, 2009; Yang, 2010)、鮐魚(yú)(Shahjahan, 2010)等腦和性腺中表達(dá)量也較高。也主要在腦和性腺中高表達(dá)，如斑馬魚(yú)(Kitahashi, 2009)、青鳉(Kitahashi, 2009)、金魚(yú)(Li, 2009)、歐洲海鱸(Felip, 2009)、塞內(nèi)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(dá)，具體表達(dá)模式具有物種特異性。

魚(yú)類基因在不同發(fā)育階段/生殖周期的表達(dá)模式也在斑馬魚(yú)等幾種魚(yú)類中有所報(bào)道。雌性斑馬魚(yú)腦表達(dá)量在孵化后逐漸升高，84 d時(shí)達(dá)到峰值；而雄性斑馬魚(yú)腦表達(dá)量在孵化后6周達(dá)到峰值，12周時(shí)有所下降(Biran, 2008)。此外，斑馬魚(yú)表達(dá)量在孵化后30 d達(dá)到峰值(Kitahashi, 2009)。上述結(jié)果顯示，可能參與了斑馬魚(yú)青春期啟動(dòng)。鮐魚(yú)腦在不同生殖周期的表達(dá)模式具有性別二態(tài)性，雄性腦表達(dá)量隨精巢發(fā)育逐漸降低，而雌性腦表達(dá)量在卵巢發(fā)育過(guò)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(dá)量隨性腺發(fā)育逐漸降低，均在產(chǎn)卵/排精后達(dá)到最小值(Selvaraj, 2010)。然而，精巢表達(dá)水平隨性腺發(fā)育逐漸升高，在精子成熟時(shí)期達(dá)到峰值；卵巢表達(dá)水平也隨性腺發(fā)育逐漸升高，在卵黃生成后期達(dá)到峰值(Selvaraj, 2010)。以上結(jié)果表明，可能參與了鮐魚(yú)季節(jié)性性腺發(fā)育。其他魚(yú)類表達(dá)水平也隨性腺發(fā)育而發(fā)生波動(dòng)(Alvarado, 2013; Migaud, 2012; Park, 2016; Saha, 2016; Shahi, 2017)。

3 魚(yú)類kissr基因類型、結(jié)構(gòu)及時(shí)空表達(dá)特性

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

4 Kisspeptin對(duì)魚(yú)類生殖調(diào)控作用研究

4.1 Kisspeptin對(duì)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(dá)調(diào)控的影響

GnRH是垂體促性腺激素合成與分泌的主要促進(jìn)因子，在每種硬骨魚(yú)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(yú)中鑒定出了基因，并進(jìn)一步證實(shí)在GnRH1、GnRH2及GnRH3神經(jīng)元中表達(dá)，這表明Kiss2能夠直接作用于GnRH神經(jīng)元，進(jìn)而影響其活性及表達(dá)調(diào)控。在青鳉中，通過(guò)電生理學(xué)研究表明，Kiss1能夠促進(jìn)GnRH3神經(jīng)元的電活動(dòng)(Electrical activity)，而河豚毒素或者阻斷突觸傳遞均降低了Kiss1誘導(dǎo)的GnRH3神經(jīng)元的電活動(dòng)，這表明Kiss1以間接方式通過(guò)突觸調(diào)控進(jìn)而激活GnRH3神經(jīng)元的電活動(dòng)(Zhao, 2012)。

4.2 Kisspeptin對(duì)垂體激素合成與分泌的影響

由于魚(yú)類中存在2種Kiss多肽，Kiss對(duì)魚(yú)類垂體激素分泌的影響更加復(fù)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(yú)血清LH水平 (Li, 2009)。但Kiss1和Kiss2均不影響金魚(yú)垂體細(xì)胞LH分泌(Li, 2009)。相反，另有研究表明，Kiss1直接促進(jìn)了金魚(yú)垂體細(xì)胞LH分泌(Chang, 2012; Yang, 2010)。最近研究報(bào)道，Kiss2而非Kiss1促進(jìn)了歐洲海鱸(Espigares, 2015b)和條紋鱸(Zmora, 2015)垂體細(xì)胞LH分泌。Kiss1和Kiss2對(duì)雜交條紋鱸LH分泌的調(diào)控作用與生殖周期相關(guān)。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?gòu)?fù)蘇期，Kiss1和Kiss2均增加了血清中LH水平(Zmora, 2012)。關(guān)于FSH分泌調(diào)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(wú)影響(Felip, 2009)。同樣，Kiss2而非Kiss1促進(jìn)了歐洲海鱸垂體細(xì)胞FSH分泌(Espigares, 2015b)。此外，Kiss1和Kiss2均促進(jìn)了條紋鱸垂體細(xì)胞FSH分泌(Zmora, 2015)。而長(zhǎng)期埋植Kiss2顯著性地降低了條紋鱸血清FSH水平(Zmora, 2014)。在魚(yú)類中，關(guān)于Kiss對(duì)GH分泌的影響僅見(jiàn)于金魚(yú)，Kiss1促進(jìn)了金魚(yú)垂體細(xì)胞GH分泌(Chang, 2012; Yang, 2010)。綜上所述，Kiss對(duì)垂體激素分泌的調(diào)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(duì)性腺發(fā)育及類固醇激素分泌的影響

5 魚(yú)類kisspeptin的信號(hào)轉(zhuǎn)導(dǎo)機(jī)制

在哺乳類中，Kiss能夠激活多種細(xì)胞內(nèi)信號(hào)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(guān)Kiss信號(hào)轉(zhuǎn)導(dǎo)機(jī)制的研究相對(duì)較少。在兩棲類中，Moon等(2009)通過(guò)CRE-luc(對(duì)應(yīng)AC/PKA通路)和SRE-luc(對(duì)應(yīng)PLC/PKC通路)報(bào)告系統(tǒng)表明，Kiss能夠激活轉(zhuǎn)染了牛蛙() Kiss2R的非洲綠猴腎纖維細(xì)胞系(CV-1 cells)中SRE-luc的活性，但對(duì)CRE-luc活性無(wú)影響。此外，PKC抑制劑GF109203X預(yù)處理CV-1細(xì)胞系顯著性地降低了Kiss誘導(dǎo)的SRE-luc的活性，而Rho激酶抑制劑Y-27632預(yù)處理CV-1細(xì)胞系部分阻斷了Kiss誘導(dǎo)的SRE-luc的活性，上述結(jié)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(yú)類kiss/kissr系統(tǒng)的表達(dá)調(diào)控研究

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

Kiss/KissR系統(tǒng)也介導(dǎo)了睪酮(Testosterone, T)對(duì)生殖軸的反饋調(diào)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(dá)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(dá)水平，卻不影響、及的表達(dá)水平(Alvarado, 2016)。然而，睪酮促進(jìn)了雄性歐洲海鱸垂體細(xì)胞及的表達(dá)水平，對(duì)的表達(dá)水平無(wú)影響(Espigares, 2015b)。此外，睪酮也不影響半滑舌鰨下丘腦中及的表達(dá)水平(Wang, 2017b)。目前，關(guān)于甲狀腺激素(Thyroid hormone)對(duì)魚(yú)類系統(tǒng)的調(diào)控作用僅見(jiàn)于羅非魚(yú)。腹腔注射甲狀腺激素，顯著地增加了羅非魚(yú)腦的表達(dá)水平，但由于甲狀腺激素受體不在Kiss2神經(jīng)元中表達(dá)，這表明甲狀腺激素是以間接的方式影響的表達(dá)(Ogawa, 2013)。綜上所述，性類固醇激素及甲狀腺激素通過(guò)影響系統(tǒng)的表達(dá)水平進(jìn)而影響魚(yú)類生殖調(diào)控。

6.2 Kisspeptin等神經(jīng)肽對(duì)kiss/kissr系統(tǒng)的調(diào)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(dòng)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(guò)其受體GnIHR (之前被稱作GPR147)介導(dǎo)作用于腦-垂體-性腺軸進(jìn)而影響動(dòng)物生殖調(diào)控(Tsutsui, 2010; Ubuka, 2016; Wang, 2018)。目前，從魚(yú)類到哺乳類都鑒定出了的同源基因，并且每種魚(yú)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(duì)的表達(dá)調(diào)控也有少數(shù)報(bào)道。在半滑舌鰨中，GnIH-1和GnIH-2均不影響下丘腦中的表達(dá)水平(劉權(quán)等, 2017)。腹腔注射斜帶石斑魚(yú)3種GnIH多肽也不影響其下丘腦的表達(dá)水平(Wang, 2015)。此外，哺乳類GnIH同源多肽RFRP3也不影響大鼠表達(dá)水平(Johnson, 2008)。盡管側(cè)腦室注射歐洲海鱸GnIH-1不影響其腦、及的表達(dá)水平，但是，GnIH-2均降低了及的表達(dá)水平，這說(shuō)明在歐洲海鱸中，GnIH-2主要發(fā)揮了生殖調(diào)控的抑制作用(Paullada-Salmeron, 2016)。

6.3 光照對(duì)kiss/kissr系統(tǒng)的調(diào)控作用

光照是影響魚(yú)類及其他脊椎動(dòng)物生殖調(diào)控的一個(gè)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(dǎo)(Kitahashi, 2013)。目前，關(guān)于光照對(duì)魚(yú)類系統(tǒng)的表達(dá)調(diào)控研究相對(duì)較少且存在爭(zhēng)議。如持續(xù)性光照降低了羅非魚(yú)腦的表達(dá)水平，表明光照能夠以直接或者間接的方式影響的表達(dá)(Martinez-Chavez, 2008)。同樣，持續(xù)性光照導(dǎo)致歐洲海鱸前中腦及的表達(dá)量不再隨季節(jié)變化而變化(Espigares, 2017)。長(zhǎng)光照(繁殖狀態(tài))條件下，青鳉下丘腦核腹側(cè)結(jié)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(jìn)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(dá)量無(wú)顯著性差異，這說(shuō)明光照不影響大西洋鱈基因表達(dá)(Cowan, 2012)。特別是褪黑激素促進(jìn)了斑馬魚(yú)腦及的表達(dá)水平(Carnevali, 2011)，卻抑制了歐洲海鱸腦及的表達(dá)水平(Alvarado, 2015)。綜上所示，Kiss/KissR系統(tǒng)可能介導(dǎo)了光照(及褪黑激素)對(duì)魚(yú)類生殖調(diào)控過(guò)程，然而具體作用機(jī)制因物種而異，需要進(jìn)一步深入研究。

6.4 溫度對(duì)kiss/kissr系統(tǒng)的調(diào)控作用

對(duì)變溫動(dòng)物而言，溫度是影響其生殖調(diào)控的一個(gè)重要環(huán)境因子。水溫升高或者降低均能抑制魚(yú)類生殖，但其分子機(jī)制仍不清楚。Kiss作為魚(yú)類生殖調(diào)控的一個(gè)重要因子，溫度對(duì)基因的表達(dá)調(diào)控作用也有了初步研究。斑馬魚(yú)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(yú)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(yú)全腦的表達(dá)量顯著性增加，高溫組的表達(dá)量與正常組相比無(wú)顯著性差異；而低溫組和高溫組斑馬魚(yú)全腦的表達(dá)量較正常組均顯著性降低(Shahjahan, 2013)。此外，低溫也增加了斑馬魚(yú)松果體等部分腦區(qū)的表達(dá)量，然而，低溫和高溫均降低了斑馬魚(yú)下丘腦等部分腦區(qū)的表達(dá)量(Shahjahan, 2013)。上述結(jié)果表明，溫度調(diào)控斑馬魚(yú)及表達(dá)的作用機(jī)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(shuō)明和系統(tǒng)可能參與了斑馬魚(yú)不同的生理功能(Shahjahan, 2013)。

同樣，將星點(diǎn)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(dá)量也顯著性降低；與此同時(shí)，低溫和高溫組均抑制了腦、垂體及的表達(dá)水平(Shahjahan, 2016)。上述結(jié)果表明，低溫和高溫組通過(guò)抑制系統(tǒng)，進(jìn)而阻斷星點(diǎn)東方鲀生殖。銀漢魚(yú)()的性別決定、分化與溫度緊密相關(guān)，低溫(17℃~19℃)導(dǎo)致100%全雌，高溫(29℃)導(dǎo)致100%全雄，而24℃~25°℃導(dǎo)致雌雄比例各半(Tovar Bohorquez, 2017)。在高溫條件下，銀漢仔魚(yú)整個(gè)腦部的表達(dá)量在孵化后4周顯著性增加；而在低溫條件下，腦部的表達(dá)量在孵化后8周內(nèi)保持不變，這表明Kiss2可能在雄性發(fā)育過(guò)程中性別決定階段發(fā)揮了重要作用(Tovar Bohorquez, 2017)。

6.5 饑餓對(duì)kiss/kissr系統(tǒng)的調(diào)控作用

營(yíng)養(yǎng)狀況也會(huì)影響動(dòng)物生殖活動(dòng)。目前，關(guān)于Kiss介導(dǎo)的能量平衡與生殖之間關(guān)系的研究較少。在哺乳類中，饑餓導(dǎo)致小鼠()下丘腦及表達(dá)量降低(Luque, 2007)。同樣，饑餓也降低了大鼠下丘腦的表達(dá)量，卻增加了的表達(dá)量(Castellano, 2005)。在魚(yú)類中，饑餓15 d導(dǎo)致塞內(nèi)加爾鰨體重減少，卻增加了下丘腦及的表達(dá)水平，但對(duì)胃中及的表達(dá)水平無(wú)影響(Mechaly, 2011)。同樣，饑餓也增加了歐洲海鱸下丘腦、、及的表達(dá)水平(Escobar, 2016)。綜上所述，饑餓對(duì)哺乳類和魚(yú)類系統(tǒng)的不同調(diào)控作用表明，該系統(tǒng)可能在哺乳類和魚(yú)類能量平衡過(guò)程中起著相反的作用。此外，Kiss/KissR系統(tǒng)是否參與了魚(yú)類攝食調(diào)控仍不得而知，需要進(jìn)一步深入研究。

7 小結(jié)

Kiss是一種多功能的神經(jīng)肽，它在下丘腦-垂體-性腺軸多個(gè)水平參與了哺乳動(dòng)物生殖調(diào)控。目前，盡管已在多種魚(yú)類中鑒定出了Kiss/KissR系統(tǒng)，但其在魚(yú)類生殖調(diào)控中的精確作用需要進(jìn)一步研究；Kiss調(diào)控垂體激素分泌及其基因表達(dá)的信號(hào)轉(zhuǎn)導(dǎo)機(jī)制網(wǎng)絡(luò)需要進(jìn)一步完善；Kiss是否參與魚(yú)類攝食調(diào)控及其作用機(jī)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(gè)水平將多種信號(hào)整合進(jìn)而調(diào)控生殖等生理過(guò)程仍不清楚，只有闡明上述機(jī)制才能更好地了解Kiss參與魚(yú)類生殖、生長(zhǎng)及代謝的協(xié)調(diào)過(guò)程。該綜述總結(jié)了魚(yú)類Kiss及其受體的研究進(jìn)展，并對(duì)Kiss的生理學(xué)功能、信號(hào)轉(zhuǎn)導(dǎo)機(jī)制以及表達(dá)調(diào)控研究進(jìn)行概括討論，增加了人們對(duì)Kiss/KissR系統(tǒng)參與魚(yú)類生殖調(diào)控機(jī)制的認(rèn)識(shí)，為后續(xù)研究提供參考。

Akazome Y, Kanda S, Okubo K,Functional and evolutionary insights into vertebrate kisspeptin systems from studies of fish brain. Journal of Fish Biology, 2010, 76(1): 161–182

Alvarado MV, Carrillo M, Felip A. Expression of kisspeptins and their receptors, gnrh-1/gnrhr-II-1a and gonadotropin genes in the brain of adult male and female European sea bass during different gonadal stages. General and Comparative Endocrinology, 2013, 187: 104–116

Alvarado MV, Carrillo M, Felip A. Melatonin-induced changes in kiss/gnrh gene expression patterns in the brain of male sea bass during spermatogenesis. Comparative Biochemistry and Physiology. Part A:Molecular and Integrative Physiology, 2015, 185: 69–79

Alvarado MV, Servili A, Moles G,Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish European sea bass. Journal of Experimental Biology, 2016, 219: 3353–3365

Beck BH, Fuller SA, Peatman E,Chronic exogenous kisspeptin administration accelerates gonadal development in basses of the genus Morone. Comparative Biochemistry and Physiology Part A:Molecular and Integrative Physiology, 2012, 162(3): 265–273

Biran J, Ben-Dor S, Levavi-Sivan B. Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates. Biology of Reproduction, 2008, 79(4): 776–786

Carnevali O, Gioacchini F, Maradonna F,Melatonin induces follicle maturation in. PLoS One, 2011, 6: e19978

Castano JP, Martinez-Fuentes AJ, Gutierrez-Pascual E,Intracellular signaling pathways activated by kisspeptins through GPR54: Do multiple signals underlie function diversity? Peptides, 2009, 30(1): 10–15

Castellano JM, Navarro VM, Fernández-Fernández R,Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology, 2005, 146(9): 3917–3925

Chang JP, Mar A, Wlasichuk M,Kisspeptin-1 directly stimulates LH and GH secretion from goldfish pituitary cells in a Ca(2+)-dependent manner. General and Comparative Endocrinology, 2012, 179(1): 38–46

Cowan M, Davie A, Migaud H. Photoperiod effects on the expression of kisspeptin and gonadotropin genes in Atlantic cod,, during first maturation. Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology, 2012, 163(1): 82–94

d'Anglemont de Tassigny X, Fagg LA, Dixon JP,Hypogonadotropic hypogonadism in mice lacking a functionalgene. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(25): 10714–10719

de Roux N, Genin E, Carel JC,Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(19): 10972–10976

Dungan HM, Clifton DK, Steiner RA. Minireview:Kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion. Endocrinology, 2006, 147(3): 1154–1158

Elizur A, Nocillado J, Biran J,Advancement of the onset of puberty inby chronic treatment with kiss peptides. Indian Journal Science Technology, 2011, 4: 274– 275

Escobar S, Felip A, Zanuy S,Is the kisspeptin system involved in responses to food restriction in order to preserve reproduction in pubertal male sea bass (). Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology, 2016, 199: 38–46

Espigares F, Carrillo M, Gomez A,The forebrain-midbrain acts as functional endocrine signaling pathway of Kiss2/Gnrh1 system controlling the gonadotroph activity in the teleost fish European sea bass (). Biology of Reproduction, 2015a, 92(3): 70

Espigares F, Rocha A, Gomez A,Photoperiod modulates the reproductive axis of european sea bass through regulation of kiss1 and gnrh2 neuronal expression. General and Comparative Endocrinology, 2017, 240: 35–45

Espigares F, Zanuy S, Gomez A. Kiss2 as a regulator of Lh and Fsh secretion via Paracrine/Autocrine signaling in the teleost fish European Sea Bass (). Biology of Reproduction, 2015b, 93(5): 114

Fairgrieve MR, Shibata Y, Smith EK,Molecular characterization of the gonadal kisspeptin system: Cloning, tissue distribution, gene expression analysis and localization in sablefish (). General and Comparative Endocrinology, 2016, 225: 212–223

Felip A, Espigares F, Zanuy S,Differential activation of kiss receptors by Kiss1 and Kiss2 peptides in the sea bass. Reproduction, 2015, 150(3): 227–243

Felip A, Zanuy S, Pineda REvidence for two distinct KiSS genes in non-placental vertebrates that encode kisspeptins with different gonadotropin-releasing activities in fish and mammals. Molecular and Cellular Endocrinology, 2009, 312(1–2): 61–71

Filby AL, van Aerle R, Duitman J,The kisspeptin/ gonadotropin-releasing hormone pathway and molecular signaling of puberty in fish. Biology of Reproduction, 2008, 78(2): 278–289

Imamura S, Hur SP, Takeuchi Y,Molecular cloning of kisspeptin receptor genes (gpr54-1 and gpr54-2) and their expression profiles in the brain of a tropical damselfish during different gonadal stages. Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology, 2016, 203: 9–16

Johnson MA, Fraley GS. Rat RFRP-3 alters hypothalamic GHRH expression and growth hormone secretion but does not affect KiSS-1 gene expression or the onset of puberty in male rats. Neuroendocrinology, 2008, 88(4): 305–315

Kanda S, Akazome Y, Matsunaga T,Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (O). Endocrinology, 2008, 149(5): 2467–2476

Kanda S, Karigo T, Oka Y. Steroid sensitive kiss2 neurones in the goldfish: evolutionary insights into the duplicate kisspeptin gene-expressing neurones. Journal of Neuroendocrinology, 2012, 24(6): 897–906

Kim NN, Choi YU, Park HS,Kisspeptin regulates the somatic growth-related factors of the cinnamon clownfish. Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology, 2015, 179: 17–24

Kitahashi T, Ogawa S, Parhar IS. Cloning and expression of kiss2 in the zebrafish and medaka. Endocrinology, 2009, 150(2): 821–831

Kitahashi T, Parhar IS. Comparative aspects of kisspeptin gene regulation. General and Comparative Endocrinology, 2013, 181(1): 197–202

Klenke U, Zmora N, Stubblefield J,Expression patterns of the kisspeptin system and GnRH1 correlate in their response to gonadal feedback in female striped bass. Indian Journal of Science Technology, 2011, 4(S8): 33–34

Kotani M, Detheux M, Vandenbogaerde A,The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry, 2001, 276(37): 34631– 34636

Lee DK, Nguyen T, O'Neill GP,Discovery of a receptor related to the galanin receptors. FEBS Letters, 1999, 446(1): 103–107

Lee JH, Miele ME, Hicks DJ,KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Journal of the National Cancer Institute, 1996, 88(23): 1731–1737

Lee JH, Welch DR. Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Research, 1997, 57(12): 2384–2387

Lee YR, Tsunekawa K, Moon MJ,Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology, 2009, 150(6): 2837–2846

Li S, Zhang Y, Liu Y,Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (). Journal of Endocrinology, 2009, 201(3): 407–418

Liu Q, Wang B, Liu XZ,. Effects of gonadotropin-inhibitory hormone peptides on the reproduction-related gene expression in the hypothalamus of half-smooth tongue sole (). Progress in Fishery Sciences, 2017, 38(1): 56–62 [劉權(quán), 王濱, 柳學(xué)周, 等GnIH 多肽對(duì)半滑舌鰨()下丘腦生殖相關(guān)基因表達(dá)的影響. 漁業(yè)科學(xué)進(jìn)展, 2017, 38(1): 56–62]

Luque RM, Kineman RD, Tena-Sempere M. Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: Analyses using mouse models and a cell line. Endocrinology, 2007, 148(10): 4601–4611

Martinez-Chavez CC, Minghetti M, Migaud H. GPR54 and rGnRH I gene expression during the onset of puberty in. General and Comparative Endocrinology, 2008, 156(2): 224–233

Mechaly AS, Vinas J, Murphy CGene structure of the Kiss1 receptor-2 (Kiss1r-2) in the Atlantic halibut: Insights into the evolution and regulation of Kiss1r genes. Molecular and Cellular Endocrinology, 2010, 317(1–2): 78–89

Mechaly AS, Vinas J, Piferrer F. Gene structure analysis of kisspeptin-2 (Kiss2) in the Senegalese sole (): Characterization of two splice variants of Kiss2, and novel evidence for metabolic regulation of kisspeptin signaling in non-mammalian species. Molecular and Cellular Endocrinology, 2011, 339(1–2): 14–24

Mechaly AS, Vinas J, Piferrer F. Identification of two isoforms of the Kisspeptin-1 receptor (kiss1r) generated by alternative splicing in a modern teleost, the Senegalese sole (). Biology of Reproduction, 2009, 80(1): 60–69

Mechaly AS, Vinas J, Piferrer F. The kisspeptin system genes in teleost fish, their structure and regulation, with particular attention to the situation in Pleuronectiformes. General and Comparative Endocrinology, 2013, 188(1): 258–268

Migaud H, Ismail R, Cowan M,Kisspeptin and seasonal control of reproduction in male European sea bass (). General and Comparative Endocrinology, 2012, 179(3): 384–399

Mitani Y, Kanda S, Akazome Y,Hypothalamic Kiss1 but not Kiss2 neurons are involved in estrogen feedback in medaka (). Endocrinology, 2010, 151(4): 1751–1759

Mohamed JS, Benninghoff AD, Holt GJ,Developmental expression of the G protein-coupled receptor 54 and three GnRH mRNAs in the teleost fish cobia. Journal of Molecular Endocrinology, 2007, 38(1–2): 235–244

Moon JS, Lee YR, Oh DY,Molecular cloning of the bullfrog kisspeptin receptor GPR54 with high sensitivity to Xenopus kisspeptin. Peptides, 2009, 30(1): 171–179

Muir AI, Chamberlain L, Elshourbagy NA,AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. Journal of Biological Chemistry, 2001, 276(31): 28969–28975

Nocillado JN, Biran J, Lee YY,The Kiss2 receptor (Kiss2r) gene in Southern Bluefin Tuna,and in Yellowtail Kingfish,-functional analysis and isolation of transcript variants. Molecular and Cellular Endocrinology, 2012, 362(1–2): 211–220

Nocillado JN, Levavi-Sivan B, Carrick F,Temporal expression of G-protein-coupled receptor 54 (GPR54), gonadotropin-releasing hormones (GnRH), and dopamine receptor D2 (drd2) in pubertal female grey mullet,. General and Comparative Endocrinology, 2007, 150(2): 278–287

Nocillado JN, Zohar Y, Biran J,Chronic kisspeptin administration stimulated gonadal development in pre-pubertal male yellowtail kingfish (; Perciformes) during the breeding and non-breeding season. General and Comparative Endocrinology, 2013, 191(9): 168–176

Ogawa S, Ng KW, Ramadasan PN,Habenular Kiss1 neurons modulate the serotonergic system in the brain of zebrafish. Endocrinology, 2012, 153(5): 2398–2407

Ogawa S, Ng KW, Xue X,Thyroid hormone upregulates hypothalamic kiss2 Gene in the male Nile tilapia,. Front Endocrinol (Lausanne), 2013, 4: 184

Ogawa S, Parhar IS. Structural and functional divergence of gonadotropin-inhibitory hormone from jawless fish to mammals. Front Endocrinol (Lausanne), 2014, 5 (5): 177

Ohga H, Fujinaga Y, Selvaraj S,Identification, characterization, and expression profiles of two subtypes of kisspeptin receptors in a scombroid fish (Chub mackerel). General and Comparative Endocrinology, 2013, 193: 130–140

Ohga H, Selvaraj S, Adachi H,Functional analysis of kisspeptin peptides in adult immature chub mackerel () using an intracerebroventricular administration method. Neuroscience Letters, 2014, 561: 203–207

Ohtaki T, Shintani Y, Honda S,Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature, 2001, 411(6837): 613–617

Onuma TA, Duan C. Duplicated Kiss1 receptor genes in zebrafish: Distinct gene expression patterns, different ligand selectivity, and a novel nuclear isoform with transactivating activity. FASEB Journal, 2012, 26(7): 2941–2950

Parhar I S, Ogawa S, Sakuma Y. Laser-captured single digoxigenin- labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (Gpr54) during maturation in cichlid fish. Endocrinology, 2004, 145(8): 3613–3618

Park JW, Jin YH, Oh SY,Kisspeptin2 stimulates the HPG axis in immature Nile tilapia (). Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2016, 202: 31–38

Pasquier J, Kamech N, Lafont AG,Molecular evolution of GPCRs: Kisspeptin/kisspeptin receptors. Journal of Molecular Endocrinology, 2014, 52(3): 101–117

Pasquier J, Lafont AG, Jeng SR,Multiple kisspeptin receptors in early osteichthyans provide new insights into the evolution of this receptor family. PLoS One, 2012, 7(11): e48931

Pasquier J, Lafont AG, Leprince J,First evidence for a direct inhibitory effect of kisspeptins on LH expression in the eel,. General and Comparative Endocrinology, 2011, 173(1): 216–225

Paullada-Salmeron JA, Cowan M, Aliaga-Guerrero MGonadotropin inhibitory hormone down-regulates thebrain- Pituitary reproductive axis of male European Sea Bass (). Biology of Reproduction, 2016, 94(6): 121

Roa J, Navarro VM, Tena-Sempere M. Kisspeptins in reproductive biology: Consensus knowledge and recent developments. Biology of Reproduction, 2011, 85(4): 650–660

Saha A, Pradhan A, Sengupta S,Molecular characterization of two kiss genes and their expression in rohu () during annual reproductive cycle. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2016, 191: 135–145

Selvaraj S, Kitano H, Fujinaga Y,Molecular characterization, tissue distribution, and mRNA expression profiles of two Kiss genes in the adult male and female chub mackerel () during different gonadal stages. General and Comparative Endocrinology, 2010, 169(1): 28–38

Selvaraj S, Ohga H, Kitano H,Peripheral administration of Kiss1 pentadecapeptide induces gonadal development in sexually immature adult scombroid fish. Zoology Science, 2013a, 30(6): 446–454

Selvaraj S, Ohga H, Nyuji M,Subcutaneous administration of Kiss1 pentadecapeptide accelerates spermatogenesis in prepubertal male chub mackerel (). Comparative Biochemistry and Physiology Part A:Molecular and Integrative Physiology, 2013b, 166(2): 228–236

Seminara SB, Messager S, Chatzidaki EE,The GPR54 gene as a regulator of puberty. New England Journal of Medicine, 2003, 349(17): 1614–1627

Servili A, Le Page Y, Leprince J,Organization of two independent kisspeptin systems derived from evolutionary- ancient kiss genes in the brain of zebrafish. Endocrinology, 2011, 152(4): 1527–1540

Shahi N, Singh AK, Sahoo M,Molecular cloning, characterization and expression profile of kisspeptin1 and kisspeptin1 receptor at brain-pituitary-gonad (BPG) axis of golden mahseer,(Hamilton, 1822) during gonadal development. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2017, 205: 13–29

Shahjahan M, Kitahashi T, Ando H. Temperature affects sexual maturation through the control of kisspeptin, kisspeptin receptor, GnRH and GTH subunit gene expression in the grass puffer during the spawning season. General and Comparative Endocrinology, 2016, 243: 138–145

Shahjahan M, Kitahashi T, Ogawa S,Temperature differentially regulates the two kisspeptin systems in the brain of zebrafish. General and Comparative Endocrinology, 2013, 193(4): 79–85

Shahjahan M, Motohashi E, Doi H,Elevation of Kiss2 and its receptor gene expression in the brain and pituitary of grass puffer during the spawning season. General and Comparative Endocrinology, 2010, 169(1): 48–57

Shi Y, Zhang Y, Li S,Molecular identification of the Kiss2/Kiss1ra system and its potential function during 17alpha-methyltestosterone-induced sex reversal in the orange-spotted grouper,. Biology of Reproduction, 2010, 83(1): 63–74

Tang H, Liu Y, Luo D,The kiss/kissr systems are dispensable for zebrafish reproduction:Evidence from gene knockout studies. Endocrinology, 2015, 156(2): 589–599

Tena-Sempere M. Roles of kisspeptins in the control of hypothalamic-gonadotropic function: Focus on sexual differentiation and puberty onset. Endocrine Development, 2010, 17: 52–62

Tena-Sempere M, Felip A, Gomez A,Comparative insights of the kisspeptin/kisspeptin receptor system:Lessons from non-mammalian vertebrates. General and Comparative Endocrinology, 2012, 175(2): 234–243

Tovar Bohorquez MO, Mechaly AS, Hughes LC,Kisspeptin system in pejerrey fish (). Characterization and gene expression pattern during early developmental stages. Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology, 2017, 204: 146–156

Tsutsui K, Bentley GE, Kriegsfeld LJ,Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: new key neuropeptides controlling reproduction. Journal of Neuroendocrinology, 2010, 22(7): 716–727

Ubuka T, Son YL, Tsutsui K. Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin- inhibitory hormone. General and Comparative Endocrinology, 2016, 227: 27–50

Um HN, Han JM, Hwang JI,Molecular coevolution of kisspeptins and their receptors from fish to mammals. Annals of the New York Academy of Sciences, 2010, 1200(1): 67–74

van Aerle R, Kille P, Lange A,Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish. Peptides, 2008, 29(1): 57–64

Wang B, Liu Q, Liu XZ,Molecular characterization of Kiss2 receptor andeffects of Kiss2 on reproduction- related gene expression in the hypothalamus of half-smooth tongue sole (). General and Comparative Endocrinology, 2017a, 249, 55–63

Wang B, Liu Q, Liu XZ,Molecular characterization and expression profiles of LPXRFa at the brain-pituitary-gonad axis of half-smooth tongue sole () during ovarian maturation. Comparative Biochemistry and Physiology. Part B: Biochemistry and Molecular Biology, 2018, 216, 59–68

Wang B, Liu Q, Liu XZ,Molecular characterization ofand differential regulation of reproduction-related genes by sex steroids in the hypothalamus of half-smooth tongue sole (). Comparative Biochemistry and Physiology. Part A: Molecular and Integrative Physiology, 2017b, 213, 46–55

Wang B, Liu XZ, Liu Q,. Molecular cloning, localization, and expression analysis ofin different tissues of half-smooth tongue sole () during ovarian maturation. Progress in Fishery Sciences, 2017, 38(1): 63–72 [王濱, 柳學(xué)周, 劉權(quán)等半滑舌鰨()基因克隆、組織分布及卵巢成熟過(guò)程中表達(dá)分析. 漁業(yè)科學(xué)進(jìn)展, 2017, 38(1): 63–72]

Wang, B, Yang, G, Liu, Q,. Inhibitory action of tongue sole LPXRFa, the piscine ortholog of gonadotropin-inhibitory hormone, on the signaling pathway induced by tongue sole kisspeptin in COS-7 cells transfected with their cognate receptors. Peptides, 2017c, 95, 62–67

Wang B, Liu XZ, Xu YJ,. Progress of research on gonadotropin-inhibitory hormone and its receptors in fish. Journal of Fisheries of China, 2016, 40(2): 278–287 [王濱, 柳學(xué)周, 徐永江, 等. 魚(yú)類促性腺激素抑制激素及其受體的研究進(jìn)展. 水產(chǎn)學(xué)報(bào), 2016, 40(2): 278–287]

Wang Q, Qi X, Guo Y,Molecular identification of GnIH/ GnIHR signal and its reproductive function in protogynous hermaphroditic orange-spotted grouper (). General and Comparative Endocrinology, 2015, 216: 9–23

Yang B, Jiang Q, Chan T,Goldfish kisspeptin: molecular cloning, tissue distribution of transcript expression, and stimulatory effects on prolactin, growth hormone and luteinizing hormone secretion and gene expression via direct actions at the pituitary level. General and Comparative Endocrinology, 2010, 165(1): 60–71

Yang Y, Gao J, Yuan C,Molecular identification of Kiss/GPR54 and function analysis with mRNA expression profiles exposure to 17alpha-ethinylestradiol in rare minnow. Molecular Biology Reports, 2016, 43(7): 739–749

Zhao Y, Wayne NL. Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin- releasing hormone neurons in medaka (). PLoS One, 2012, 7(5): e37909

Zmora N, Stubblefield J, Golan M,The medio-basal hypothalamus as a dynamic and plastic reproduction-related kisspeptin-gnrh-pituitary center in fish. Endocrinology, 2014, 155(5): 1874–1886

Zmora N, Stubblefield J, Zulperi Z,Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, morone species. Biology of Reproduction, 2012, 86(6): 177

Zmora N, Stubblefield JD, Wong TT,Kisspeptin antagonists reveal kisspeptin 1 and kisspeptin 2 differential regulation of reproduction in the teleost,. Biology of Reproduction, 2015, 93(3): 76

Zohar Y, Munoz-Cueto JA, Elizur A,Neuroendocrinology of reproduction in teleost fish. General and Comparative Endocrinology, 2010, 165(3): 438–455

(編輯 陳嚴(yán))

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(guó)水產(chǎn)科學(xué)研究院基本科研業(yè)務(wù)費(fèi)(2017HY-XKQ01; 2017GH05; 2018GH17)、中國(guó)水產(chǎn)科學(xué)研究院黃海水產(chǎn)研究所基本科研業(yè)務(wù)費(fèi)(20603022016018)、國(guó)家自然科學(xué)基金(31602133；31502145)、山東省自然科學(xué)基金(ZR2016CB02)和國(guó)家海水魚(yú)類產(chǎn)業(yè)技術(shù)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(xué)周，E-mail: liuxz@ysfri.ac.cn

# 共同第一作者

柳學(xué)周，研究員，E-mail: liuxz@ysfri.ac.cn

2017-04-24,

2017-05-18

王濱, 柳學(xué)周, 徐永江, 史寶, 劉權(quán). Kisspeptin對(duì)魚(yú)類生殖軸的調(diào)控機(jī)制研究. 漁業(yè)科學(xué)進(jìn)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