Department of Fish Physiology and Biotechnology, Instituto de Acuicultura de Torre de la Sal, 12595 Torre de la Sal, Ribera de Cabanes, Castellón, Spain.
J Exp Biol. 2009 Dec;212(Pt 23):3901-10. doi: 10.1242/jeb.035121.
The melanocortin 5 receptor (MC5R) plays a key role in the regulation of exocrine secretion in mammalian species. This receptor has also been characterized in some fish species but its function is unknown. We report the molecular and pharmacological characterization, as well as the tissue expression pattern, of sea bass MC5R. Cloning of five active alleles showing different levels of sensitivity to endogenous melanocortin and one non-functional allele demonstrate the allelic complexity of the MC5R locus. The sea bass receptor was activated by all the melanocortins tested, with ACTH and desacetyl-MSH and beta-MSH showing the lowest efficiency. The acetylation of the MSH isoforms seems to be critical for the effectiveness of the agonist. Agouti-related protein had no effect on basal or agonist-stimulated activation of the receptor. SbMC5R was mainly expressed in the brain but lower expression levels were found in several peripheral tissues, including liver. Progressive fasting did not induce up- or downregulation of hypothalamic MC5R expression, suggesting that central MC5R is not involved in the regulation of food intake in the sea bass. MTII, a sbMC5R agonist, stimulated hepatic lipolysis in vitro, measured as free fatty acid release into the culture medium after melanocortin agonist exposure of liver fragments, suggesting that MC5R is involved in the regulation of hepatic lipid metabolism. Taken together, the data suggest that different allelic combinations may confer differential sensitivity to endogenous melanocortin in tissues where MC5R is expressed and, by extension, in hepatic lipid metabolism.
黑皮质素 5 受体（MC5R）在哺乳动物物种的外分泌分泌调节中发挥关键作用。该受体在一些鱼类物种中也已被描述，但它的功能尚不清楚。我们报告了鲈鱼 MC5R 的分子和药理学特征，以及组织表达模式。克隆了五个表现出对内源性黑皮质素不同敏感性的活性等位基因和一个非功能等位基因，证明了 MC5R 基因座的等位基因复杂性。鲈鱼受体被所有测试的黑皮质素激活，ACTH 和去乙酰基-MSH 和 β-MSH 显示出最低的效率。MSH 同工型的乙酰化对于激动剂的有效性似乎至关重要。阿黑皮素原对受体的基础或激动剂刺激激活没有影响。SbMC5R 主要在脑中表达，但在包括肝脏在内的几种外周组织中发现较低的表达水平。逐渐禁食不会诱导下丘脑 MC5R 表达的上调或下调，这表明中枢 MC5R 不参与鲈鱼的摄食调节。MTII，一种 sbMC5R 激动剂，在体外刺激肝脂肪分解，测量为暴露于黑素皮质素激动剂后肝片段中释放到培养基中的游离脂肪酸，这表明 MC5R 参与调节肝脂质代谢。总之，这些数据表明，不同的等位基因组合可能在表达 MC5R 的组织中赋予对内源性黑皮质素的不同敏感性，并且可以扩展到肝脂质代谢。
