AUTHOR=Zhang Kai-Qiang , Hou Zhi-Shuai , Wen Hai-Shen , Li Yun , Qi Xin , Li Wen-Juan , Tao Ya-Xiong 

TITLE=Melanocortin-4 Receptor in Spotted Sea Bass, Lateolabrax maculatus: Cloning, Tissue Distribution, Physiology, and Pharmacology

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00705

DOI=10.3389/fendo.2019.00705

ISSN=1664-2392

ABSTRACT=<p>Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes including energy homeostasis, reproduction, sexual function, and other functions in mammals. Recent studies suggested that teleost MC4Rs have different physiological functions and pharmacological characteristics when compared to mammalian MC4Rs. In this study, we investigated spotted sea bass (<italic>Lateolabrax maculatus</italic>) MC4R (<italic>Lm</italic>MC4R) physiology and pharmacology. Spotted sea bass <italic>mc4r</italic> consisted of a 984 bp open reading frame encoding a protein of 327 amino acids. <italic>Lm</italic>MC4R was homologous to those of several teleost MC4Rs and human MC4R (hMC4R). qRT-PCR and <italic>in situ</italic> hybridization revealed that <italic>mc4r</italic> transcripts were highly expressed in the brain, followed by pituitary and liver. Brain <italic>mc4r</italic> transcripts were down-regulated in long-term and short-term fasting challenges. <italic>Lm</italic>MC4R was a functional receptor with lower maximal binding and higher basal activity than hMC4R. THIQ was not able to displace <sup>125</sup>I-NDP-MSH but could affect intracellular cAMP accumulation, suggesting that it was an allosteric ligand for <italic>Lm</italic>MC4R. <italic>In vitro</italic> studies with spotted sea bass brain cells indicated that mRNA levels of <italic>neuropeptide Y</italic> and <italic>Agouti-related peptide</italic> were down-regulated by α-MSH. In summary, we cloned spotted sea bass MC4R, and showed that it had different pharmacological properties compared to hMC4R, and potentially different functions.</p>