溫海深 張 瑩 馮啟超 侯志帥 齊 鑫 李 昀

α-黑素細(xì)胞刺激素及黑皮質(zhì)素受體-4在能量平衡和繁殖中的功能研究*

溫海深1①張 瑩1馮啟超2侯志帥1齊 鑫1李 昀1

(1. 中國海洋大學(xué) 海水養(yǎng)殖教育部重點(diǎn)實(shí)驗(yàn)室 青島 266003；2. 全國水產(chǎn)技術(shù)推廣總站 北京 100125)

阿片黑素促皮質(zhì)激素原(POMC)是黑皮質(zhì)激素的前體物質(zhì)，在機(jī)體中廣泛分布。近年來，POMC及其衍生物黑素細(xì)胞刺激素(MSH)和黑皮質(zhì)素受體-4(MC4R)在能量穩(wěn)態(tài)和繁殖活動(dòng)中的作用備受關(guān)注。研究發(fā)現(xiàn)，POMC神經(jīng)元及其加工后的產(chǎn)物對攝食和體重的調(diào)節(jié)具有重要作用。此外，POMC神經(jīng)元在下丘腦中與GnRH神經(jīng)元緊密接觸，由其產(chǎn)生的神經(jīng)遞質(zhì)和神經(jīng)肽可能對GnRH神經(jīng)元具有重要的輸入作用，從而直接或間接地調(diào)控下丘腦–垂體–性腺軸(HPG)中繁殖相關(guān)激素的合成并影響生殖活動(dòng)。本文綜述了黑皮質(zhì)素系統(tǒng)對能量穩(wěn)態(tài)和繁殖活動(dòng)的調(diào)控作用以及目前MC4R在硬骨魚類中的藥理學(xué)研究，以期其能夠在動(dòng)物的生長發(fā)育和繁殖中具有應(yīng)用前景。

阿片黑素促皮質(zhì)激素原；α-黑素細(xì)胞刺激素；黑皮質(zhì)素受體-4；能量穩(wěn)態(tài)；繁殖

近年來，黑皮質(zhì)素(Melanocyte-stimulating hormone,MSH)系統(tǒng)備受關(guān)注，作為阿片黑素促皮質(zhì)激素原(POMC)衍生物，在色素沉著、攝食、能量穩(wěn)態(tài)、免疫調(diào)節(jié)以及繁殖活動(dòng)中起著重要的作用(史學(xué)營等, 2015; Chen, 2017; Carter, 2018; Clément, 2018; Matsuda, 2018)，特別是其對能量平衡的調(diào)節(jié)作用，使之成為研究熱點(diǎn)。通過定位POMC神經(jīng)元及其衍生物在下丘腦中的分布位置及配受體結(jié)合的藥理學(xué)分析(Tao, 2010)，發(fā)現(xiàn)黑皮質(zhì)素系統(tǒng)可能通過調(diào)節(jié)下丘腦–垂體–性腺軸(HPG)從而對垂體中促性腺激素(Gth)的合成產(chǎn)生影響以調(diào)節(jié)生殖活動(dòng)。然而，此類研究多集中于哺乳動(dòng)物中，缺乏在低等脊椎動(dòng)物中的相關(guān)研究。本文基于黑皮質(zhì)素系統(tǒng)在物種間的保守性以及當(dāng)前研究中對其在能量穩(wěn)態(tài)和繁殖活動(dòng)中的調(diào)控實(shí)驗(yàn)，重點(diǎn)論述了POMC、α-黑素細(xì)胞刺激素(α-MSH)以及黑皮質(zhì)素受體-4(MC4R)在哺乳動(dòng)物和魚類中對能量穩(wěn)態(tài)和繁殖活動(dòng)的調(diào)節(jié)作用。

1 阿片黑素促皮質(zhì)激素原

POMC是黑皮質(zhì)激素的前體物質(zhì)，在機(jī)體中分布廣泛，在腦、垂體和性腺中均有表達(dá)，特別是下丘腦弓狀核中有大量表達(dá)(Kineman, 1989; 杜富寬等, 2017)，經(jīng)組織特異性轉(zhuǎn)錄調(diào)控加工成不同的衍生物。

1.1 POMC在能量穩(wěn)態(tài)中的作用

POMC神經(jīng)元作為能量穩(wěn)態(tài)的中央調(diào)節(jié)器(Cone, 1999)，對攝食和能量平衡的調(diào)控作用一直備受關(guān)注。Cheung等(1997)在弓狀核的POMC神經(jīng)元中檢測到瘦素表達(dá)；Caron等(2018)發(fā)現(xiàn)動(dòng)物處于饑餓狀態(tài)時(shí)，瘦素和POMC表達(dá)水平下降，攝食量增加。POMC與肥胖息息相關(guān)，研究發(fā)現(xiàn)，POMC突變患者出現(xiàn)早發(fā)性肥胖(Krude, 1998)；敲除POMC后，采用瘦素治療也不能降低體重(Chhabra, 2016)。由此說明，POMC可能作為瘦素調(diào)控能量穩(wěn)態(tài)的中間介質(zhì)調(diào)節(jié)攝食和體重。

圖1 POMC翻譯后加工產(chǎn)物

1.2 POMC在繁殖活動(dòng)中的功能

POMC除在能量調(diào)控中發(fā)揮重要作用外，在生殖活動(dòng)中的作用也不可忽視。光鏡和電鏡下觀察到GnRH的軸突末端與POMC細(xì)胞體并置(Sotonyi, 2010)。POMC神經(jīng)元還可能通過Kisspeptin中間神經(jīng)元影響GnRH的表達(dá)(Backholer, 2010)。Higo等(2016)在下丘腦弓狀核中定位Kisspeptin發(fā)現(xiàn)，Kiss1r表達(dá)神經(jīng)元中分布著大約63%的POMC神經(jīng)元。因此，POMC與GnRH神經(jīng)元在腦中的位置分布表明，POMC神經(jīng)元可能對GnRH神經(jīng)元具有重要的輸入作用，它能夠直接或間接地參與中樞神經(jīng)系統(tǒng)中生殖功能的調(diào)控。目前，已通過腦內(nèi)室注射(Intra- cerebroventricular injection, ICV)和基因敲除技術(shù)對POMC神經(jīng)元在HPG軸中的作用進(jìn)行探究。大鼠() ICV注射促性腺激素抑制激素(GnIH)降低了GnRH和POMC的表達(dá)水平(司麗娜等, 2017)；POMC基因敲除小鼠()的產(chǎn)仔率有顯著下降(Faulkner, 2015)，POMC可能通過與GnRH神經(jīng)元相互聯(lián)系，從而調(diào)控HPG軸中激素的合成而影響繁殖。

除神經(jīng)肽外，POMC神經(jīng)元釋放的神經(jīng)遞質(zhì)GABA和谷氨酸也顯示出了對GnRH神經(jīng)元的調(diào)節(jié)作用(Kuehl-Kovarik, 2002)。綜上，POMC神經(jīng)元及其釋放的神經(jīng)肽和神經(jīng)遞質(zhì)均可能通過直接或間接的作用調(diào)節(jié)GnRH的表達(dá)，進(jìn)而作用于繁殖功能，但此類研究目前多集中在哺乳動(dòng)物中，且其作用機(jī)制還有待進(jìn)一步研究。

2 黑素細(xì)胞刺激素(α-MSH)

MSH包含α-、β-、γ-和δ-MSH，由POMC經(jīng)組織特異性翻譯加工而成，對色素沉著、攝食和能量穩(wěn)態(tài)、免疫調(diào)節(jié)以及繁殖等生理活動(dòng)具有重要作用(Cone,2006; 朱學(xué)武等, 2017)。由于γ-MSH與受體的結(jié)合率較低(Tao, 2010)，δ-MSH僅在軟骨魚中發(fā)現(xiàn)(Dores, 2003)，且β-MSH發(fā)現(xiàn)時(shí)間較晚(Mayer, 2005)，對此研究較少。目前，關(guān)于黑素細(xì)胞刺激素的研究多集中于α-MSH。因此，本文僅論述了α-MSH對能量穩(wěn)態(tài)和繁殖活動(dòng)的調(diào)控作用。研究表明，α-MSH在中樞神經(jīng)系統(tǒng)表達(dá)量較高，主要包括背側(cè)、外側(cè)下丘腦以及弓狀核(包新民等, 1990)。同時(shí)，在垂體、皮膚、胃腸道及性腺中也檢測到α-MSH的分布，但表達(dá)量較低(Bardin, 1987; 何英等, 2013)。

2.1 α-MSH在能量穩(wěn)態(tài)中的功能

哺乳動(dòng)物中，Leptin-Melanocortin系統(tǒng)是調(diào)控能量平衡的重要系統(tǒng)。脂肪組織分泌的瘦素穿過血腦屏障，與位于下丘腦(特別是弓狀核)的瘦素受體結(jié)合(Lee, 2009)。此后，瘦素受體激活α-MSH神經(jīng)元活性，刺激下丘腦弓狀核分泌α-MSH。與此同時(shí)，分泌刺鼠相關(guān)蛋白(Agouti-related protein, AgRP)的神經(jīng)元被抑制，AgRP的合成與分泌減少(Ramos-Molina, 2016)。α-MSH和AgRP具有相互拮抗的生理功能，二者的動(dòng)態(tài)平衡是有機(jī)體保證能量平衡的重要保障之一(圖2)。

魚類中α-MSH相關(guān)研究結(jié)果與哺乳動(dòng)物一致。α-MSH合成障礙的虹鱒出現(xiàn)食欲亢進(jìn)、肝臟腫大和腹腔脂肪堆積現(xiàn)象(Yada, 2002)。給予金魚()ICV注射NDP-α-MSH(α-MSH的高效類似物)，觀察到劑量依賴性的抑制食物攝入，且在中腦定位到了α-MSH的免疫性反應(yīng)，發(fā)現(xiàn)α-MSH可能通過促腎上腺皮質(zhì)激素釋放激素(CRH)信號通路抑制食物攝入(Cerdá-Reverter, 2003a; Matsuda, 2008)。

圖2 瘦素–黑皮質(zhì)素調(diào)控能量代謝

2.2 α-MSH在繁殖活動(dòng)中的功能

α-MSH也參與繁殖活動(dòng)的調(diào)控，早期研究多集中在哺乳動(dòng)物中。用α-MSH多肽刺激小鼠卵巢，卵巢內(nèi)孕酮(P)含量顯著增加(Durando, 1998)；ICV注射α-MSH能夠影響小鼠的性行為(Thody, 1979)，并且能夠降低卵巢摘除小鼠中下丘腦和垂體組織中的GnRH、LH和FSH的表達(dá)水平(楊松鶴等, 2010)。隨后發(fā)現(xiàn)，α-MSH緊鄰GnRH和Kisspeptin神經(jīng)元(Cardoso, 2015)，α-MSH處理可以激活70%的GnRH神經(jīng)元(Roa, 2012)。上述實(shí)驗(yàn)證實(shí)，α-MSH除可以在中樞神經(jīng)系統(tǒng)和外周組織中直接調(diào)控HPG軸，也可通過Kisspeptin間接調(diào)控生殖活動(dòng)。

硬骨魚類中的研究證實(shí)，α-MSH在魚類中同樣能夠調(diào)控HPG軸，表明其調(diào)控繁殖的生理功能具有物種間的保守性。在歐洲狼鱸()和黑鯛()的卵泡顆粒細(xì)胞及卵原細(xì)胞的胞漿中發(fā)現(xiàn)α-MSH，且在繁殖期表達(dá)水平最高(Mosconi, 1994)，推測α-MSH在魚類卵巢組織中可能直接調(diào)控性類固醇激素的合成，從而影響卵泡成熟和排卵。

3 黑皮質(zhì)素受體-4(MC4R)

黑皮質(zhì)素受體-4(Melanocortin-4 receptor, MC4R)主要在下丘腦的室旁核(Paraventricular nucleus, PVN)表達(dá)。作為α-MSH的重要受體之一，能夠調(diào)控?cái)z食與能量穩(wěn)態(tài)、糖類與脂質(zhì)代謝、心血管功能和繁殖等多種生理活動(dòng)(Chen, 2017; Huszar, 1997; Nogueiras, 2007; da Silva, 2008)。人類的MC4R由332個(gè)氨基酸編碼而成，是典型的G蛋白偶聯(lián)受體(GPCR)，具有7個(gè)跨膜螺旋結(jié)構(gòu)域(Gantz, 1993)，其N端和C端分別位于細(xì)胞外和細(xì)胞內(nèi)，內(nèi)環(huán)和外環(huán)較短，使之成為GPCR超家族中最短的成員之一(Tao, 2010)。目前，已在人、狗、貓、豬等哺乳類動(dòng)物和魚、雞、鴿子等非哺乳動(dòng)物中克隆得到MC4R序列(Tao, 2010)，其在物種間高度保守。除MC4R外，在高等哺乳動(dòng)物中，還觀察到MC3R也是α-MSH的受體。MC3R與MC4R在下丘腦中高水平表達(dá)，共同參與能量調(diào)節(jié)，二者的功能并不重合。MC3R主要調(diào)節(jié)攝食行為和攝食效率，而MC4R主要調(diào)節(jié)攝食量和能量消耗(Tao, 2010)。在硬骨魚類中，早期觀點(diǎn)認(rèn)為，硬骨魚類的MC3R在進(jìn)化過程中丟失，僅保留MC4R調(diào)控魚類的能量代謝(Cortés, 2014)。近年來，部分硬骨魚類的基因組數(shù)據(jù)鑒定出MC3R(Logan, 2003)，但其生理學(xué)功能與藥理學(xué)特征尚需進(jìn)一步研究。

3.1 MC4R信號通路

MC4R的經(jīng)典信號通路是與異源G蛋白三聚體偶聯(lián)(Mountjoy, 2001)，MC4R被激動(dòng)劑，如α-MSH、β-MSH、g-MSH、ACTH激活后，引起環(huán)腺苷酸環(huán)化酶(Adenylate cyclase, AC)活化，使細(xì)胞內(nèi)環(huán)磷酸腺苷酸(Cyclic adenosine monophosphate, cAMP)增加，進(jìn)而激活下游的蛋白激酶A(PKA)，PKA催化蛋白質(zhì)的磷酸化，進(jìn)而調(diào)控蛋白質(zhì)功能。與此同時(shí)，被PKA激活的某些蛋白可以作為轉(zhuǎn)錄因子，進(jìn)入細(xì)胞核激活或抑制相關(guān)基因的轉(zhuǎn)錄，從而調(diào)節(jié)細(xì)胞功能。除GPCRs經(jīng)典的Gs-cAMP-PKA通路外，MC4R還能夠激活絲裂原活化蛋白激酶–細(xì)胞外信號調(diào)節(jié)激酶(MEK-ERK1/2)信號通路。早期實(shí)驗(yàn)觀察到，MTⅡ誘導(dǎo)的抑制食物攝入依賴于MEK-ERK1/2信號通路(Sutton, 2005)。在穩(wěn)定表達(dá)的人MC4R的中國倉鼠卵巢(Chinese hamster ovary, CHO)細(xì)胞中，MEK- ERK1/2信號通路可以被NDP-α-MSH激活，并表現(xiàn)出時(shí)間和劑量依賴性(Vongs, 2004)，從而調(diào)節(jié)下游蛋白功能或相關(guān)基因的轉(zhuǎn)錄。

3.2 MC4R組織分布

MC4R研究較為廣泛，早期在小鼠的丘腦、下丘腦及海馬體中觀察到了MC4R的分布(Mountjoy, 1994)。后續(xù)研究發(fā)現(xiàn)，MC4R不僅存在于中樞神經(jīng)系統(tǒng)中，也在外周組織中表達(dá)。哺乳動(dòng)物中，MC4R在腦中的表達(dá)量顯著高于其他組織，外周組織如在小鼠、山羊和豬的性腺、肌肉、腎和心臟中也有少量表達(dá)(Mountjoy, 2003; 張子軍等, 2012; 何夏萍等, 2013)。禽類中，MC4R在腦中與外周組織中的表達(dá)量差異不顯著，在雞、鴨、鵝的腦、脂肪、腎、胃和腸中均有較高表達(dá)(Takeuchi, 1998; 王婕等, 2011; 原昊等, 2011)。MC4R在低等脊椎動(dòng)物中的組織表達(dá)模式區(qū)別較大。例如，角鯊()的MC4R只在腦中表達(dá)(Ringholm, 2003)，而在其他多種魚類中，除在腦中表達(dá)外，外周組織中也檢測到了MC4R的分布，如金魚(Cerdá-Reverter, 2003a)、條斑星鰈()(Kobayashi, 2008)、花鱸()(Zhang, 2019)及金錢魚()(Li, 2016)的性腺、肝臟和垂體中均有MC4R的表達(dá)。然而，MC4R在斑馬魚()的眼中也有分布(Ringholm, 2002)，而上述魚類的眼中未檢測到MC4R的表達(dá)。MC4R在腦、胃、腸中的分布，表明其能夠參與攝食和能量穩(wěn)態(tài)的調(diào)控作用。在哺乳動(dòng)物和魚類中性腺的分布，推測其可能對生殖活動(dòng)產(chǎn)生影響。但MC4R的表達(dá)具有一定的組織特異性及物種特異性，其在外周組織中的功能還有待進(jìn)一步研究。

3.3 MC4R在能量穩(wěn)態(tài)中的功能

MC4R作為瘦素介導(dǎo)食欲調(diào)節(jié)的最末端基因，在攝食和能量穩(wěn)態(tài)中的功能備受關(guān)注。Huszar等(1997)發(fā)現(xiàn)，敲除MC4R基因的小鼠食欲旺盛，體重增加。Williams等(2002)將MC4R的激動(dòng)劑MTⅡ?qū)π∈筮M(jìn)行ICV注射，發(fā)現(xiàn)其能抑制攝食，而隨后注射的抑制劑SHU9119緩解了這一現(xiàn)象。在瘦素基因敲除的小鼠中注射MC4R的激動(dòng)劑，觀察到小鼠食欲減退，體重下降(Clément, 2018)。上述研究表明，MC4R不但在瘦素調(diào)控能量穩(wěn)態(tài)的過程中起到中間介質(zhì)的作用，還能夠直接調(diào)控?cái)z食、減少體重。

在硬骨魚中關(guān)于MC4R對攝食的調(diào)控也有研究。給予金魚和虹鱒ICV注射MTⅡ，觀察到食物攝入被抑制；而注射MC4R特異性拮抗劑HS024會增加食物攝入(Cerdá-Reverter, 2003b; Schjolden, 2009)。齊口裂腹魚(在處于食物短缺環(huán)境中的墨西哥洞穴魚()中發(fā)現(xiàn)，其MC4R基因的保守殘基出現(xiàn)了突變，該突變增加了墨西哥洞穴魚抗饑餓的能力以及對黑暗環(huán)境的適應(yīng)能力(Aspiras, 2015)。此外，在MC4R的藥理學(xué)研究中發(fā)現(xiàn)，MC4R的反向激動(dòng)劑(Inverse agonist)可以降低魚類MC4R的組成性活性，刺激魚類攝食，為養(yǎng)殖帶來更高的效益。在黃鱔()中發(fā)現(xiàn)1種小分子物質(zhì)ML00253764，可以作為MC4R的反向激動(dòng)劑(Yi, 2018)。小分子配體可以直接與餌料混合，避免肌肉注射對魚類的脅迫。然而，目前ML00253764的生產(chǎn)成本較高，制約了其在養(yǎng)殖中的應(yīng)用(Yi, 2018)。如若今后可以鑒定出廉價(jià)、高效的魚類MC4R小分子反向激動(dòng)劑，則有進(jìn)一步應(yīng)用前景。

3.4 MC4R在繁殖活動(dòng)中的功能

MC4R在繁殖調(diào)控中的生理功能研究較少，且主要集中在哺乳動(dòng)物中。實(shí)驗(yàn)發(fā)現(xiàn)，AgRP過表達(dá)導(dǎo)致成年小鼠不育(Granholm, 1986)；通過基因敲降技術(shù)得到的MC4R缺陷的雄性小鼠除表現(xiàn)出肥胖外，其勃起功能受損，性行為受到影響(van der Ploeg, 2002)；MC4R缺陷雌性小鼠發(fā)情周期不規(guī)律(Chen, 2017)，且出現(xiàn)排卵率和受精率下降及早衰現(xiàn)象(Sandrock, 2009)。為進(jìn)一步明確MC4R是否參與繁殖過程，對妊娠小鼠下丘腦弓狀核中MC4R的含量進(jìn)行了測定，結(jié)果顯示，在妊娠早期，MC4R的表達(dá)量較高，隨著妊娠進(jìn)行，表達(dá)水平下降(Asadi- Yousefabad, 2015)，表明MC4R除影響性功能及性行為外，也參與到妊娠的維持過程。但Stanley等(1999)研究發(fā)現(xiàn)，給予小鼠ICV注射MC4R的抑制劑刺鼠相關(guān)蛋白(AgRP)后，GnRH、LH和FSH的表達(dá)水平上升，且在小鼠子宮內(nèi)，MC4R和雌激素(E2)呈負(fù)相關(guān)(Cheung, 2001)。這與之前所述結(jié)果不同，可能與MC4R激動(dòng)劑或抑制劑的處理濃度相關(guān)，然而具體原因還未得到實(shí)驗(yàn)驗(yàn)證，有待進(jìn)一步探究。

在硬骨魚中(如條斑星鰈、金魚、金錢魚)，大量實(shí)驗(yàn)觀察到MC4R在性腺中表達(dá)量較高(Cerdá- Reverter, 2003a; Li, 2016; Kobayashi, 2008)，推測其參與繁殖調(diào)控。同時(shí)，近期實(shí)驗(yàn)觀察到黃鱔MC4R的表達(dá)具有性別特異性。雌性黃鱔腦和性腺的MC4R基因表達(dá)顯著高于雄性，推測MC4R參與大腦雌雄二象性的調(diào)控和性腺的分化與發(fā)育(Yi, 2018)。此外，在金錢魚中，使用MC4R的激動(dòng)劑THIQ刺激體外培養(yǎng)的腦和垂體，發(fā)現(xiàn)其能夠促進(jìn)GnRH、LHβ和FSHβ的表達(dá)，而拮抗劑SHU9119作用相反，表明MC4R除能夠作用于GnRH調(diào)控生殖活動(dòng)外，也可以直接作用于垂體調(diào)節(jié)Gth的分泌(Jiang, 2017)。

3.5 MC4R的其他生理功能

哺乳動(dòng)物中，對MC4R的研究較為廣泛，除上述在能量穩(wěn)態(tài)和繁殖活動(dòng)中的調(diào)控作用外，其在心血管系統(tǒng)及糖類和脂質(zhì)代謝中的功能也受到關(guān)注，如注射MC4R拮抗劑的小鼠和獼猴()心率和動(dòng)脈壓下降(Tallam, 2004; Kievit, 2013)，MC4R敲除小鼠脂質(zhì)的吸收和甘油三酸酯的合成增加，白色脂肪組織中脂肪積累，而注射MTⅡ的小鼠脂肪利用率增加，脂肪形成減少(Nogueiras, 2007)。由于魚類在生理結(jié)構(gòu)上與哺乳動(dòng)物有較大差別，其組織和器官的分化不顯著，目前，在魚類中未有關(guān)于MC4R在心血管系統(tǒng)及糖類和脂質(zhì)代謝中功能的研究。

4 總結(jié)與展望

黑皮質(zhì)素系統(tǒng)在色素沉著、攝食和能量穩(wěn)態(tài)、免疫調(diào)節(jié)以及繁殖等生理活動(dòng)中具有重要作用。目前，關(guān)于黑皮質(zhì)素系統(tǒng)中α-MSH和MC4R對能量穩(wěn)態(tài)和繁殖活動(dòng)調(diào)控作用的研究和應(yīng)用還不充分，仍存在較多未知。能否開發(fā)出廉價(jià)的新型小分子配體作為MC4R的反向激動(dòng)劑，促進(jìn)養(yǎng)殖動(dòng)物增加體重？MC4R被配體激活后對HPG軸是否存在負(fù)反饋調(diào)控？MC4R在種間的組織表達(dá)模式存在較大差異，其對繁殖活動(dòng)的調(diào)控能力是否存在物種特異性？隨著基因敲除技術(shù)和藥理學(xué)的不斷發(fā)展，今后可以更加深入地探索其在能量穩(wěn)態(tài)和繁殖活動(dòng)中的調(diào)節(jié)通路和作用機(jī)理，并將研究結(jié)果充分應(yīng)用于實(shí)際生產(chǎn)，以期其在動(dòng)物的生長發(fā)育和遺傳育種中具有更加廣闊的應(yīng)用前景。

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The Functions of α-Melanocyte Stimulating Hormone and Melanocortin-4 Receptor During Energy Homeostasis and Reproduction

WEN Haishen1①, ZHANG Ying1, FENG Qichao2, HOU Zhishuai1, QI Xin1, LI Yun1

(1. Ocean University of China, Key Laboratory of Mariculture, Ministry of Education, Qingdao 266003; 2. National Fisheries Technology Extension Center, Beijing 100125)

Melanocortins are the products of the precursor protein proopiomelanocortin (POMC) with extensive localization in the central nervous system and peripheral tissues. Melanocortins play important roles in the skin, stress response, immune system, feeding behavior, and sexual function. In recent years, thea-melanocyte stimulating hormone (a-MSH) and melanocortin-4 receptor (MC4R) have received considerable attention for their regulation of energy homeostasis and reproduction. Previous studies have shown that POMC,a-MSH, and MC4R regulate food intake and the reproductive system by mediating the secretion of hormones related to the hypothalamic-pituitary-gonadal (HPG) axis. In this review, we summarize the physiological functions of POMC,a-MSH, and MC4R in energy homeostasis and reproduction. We also summarize the results of several studies reporting the pharmacological characteristics of teleost MC4R and discuss the potential commercial applications in aquaculture.

Proopiomelanocorin;a-Melanocyte stimulating hormone; Melanocortin-4 receptor; Energy homeostasis; Reproduction

WEN Haishen, E-mail: wenhaishen@ouc.edu.cn

S961

A

2095-9869(2020)03-0176-08

10.19663/j.issn2095-9869.20200218001

http://www.yykxjz.cn/

* 國家自然科學(xué)基金項(xiàng)目(41676216; 41976089)資助[This work was supported by National Natural Science Foundation of China (41676216; 41976089)]

溫海深，教授，E-mail: wenhaishen@ouc.edu.cn

2020-02-18,

2020-03-23

溫海深, 張瑩, 馮啟超, 侯志帥, 齊鑫, 李昀. α-黑素細(xì)胞刺激素及黑皮質(zhì)素受體-4在能量平衡和繁殖中的功能研究. 漁業(yè)科學(xué)進(jìn)展, 2020, 41(3): 176–183

Wen HS, Zhang Y, Feng QC, Hou ZS, Qi X, Li Y. The functions of α-melanocyte stimulating hormone and melanocortin-4 receptor during energy homeostasis and reproduction. Progress in Fishery Sciences, 2020, 41(3): 176–183

(編輯 馬璀艷)