Abstract
The activation of melanocortin 2 receptor (MC2R) by ACTH mediates the signaling cascade leading to steroid synthesis in the interrenal tissue (analogous to the adrenal cortex in mammals) of fish. However, little is known about the functional regulation of this receptor in fish. In this work described, we cloned sea bass MC2R from a liver cDNA. SbMC2R requires the melanocortin 2 receptor accessory protein (MRAP) for its functional expression. Dietary cortisol but not long-term stress protocols downregulated interrenal sbMC2R expression. Data suggest the existence of a negative feedback on interrenal sbMC2R expression imposed by local or systemic glucocorticoids. This feedback could be involved in long-term stress adaptation by regulating interrenal sensitivity to ACTH. ACTH-induced MC2R activation stimulates hepatic lipolysis, suggesting that ACTH may mediate stress-induced effects upstream of cortisol release.
Highlights
Melanocortin peptides are processed from the complex peptide precursor named proopiomelanocortin (POMC)
Molecular cloning sbMC2R By means of RT-PCR and using degenerate primers designed against conserved regions of fish melanocortin receptor sequences, we cloned a 214 bp fragment showing high identity to the melanocortin 2 receptor (MC2R) reported in other vertebrate species
Similar to other melanocortin receptors, the sbMC2R orthologue exhibits short extracellular (ECL) and intracellular (ICL) loops, and shares cysteine residues at positions 234, 248 and 254, which are fully conserved in all melanocortin receptors (Fig. 1 and http://www.gpcr.org)
Summary
Melanocortin peptides are processed from the complex peptide precursor named proopiomelanocortin (POMC). They are mainly comprised of adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormones (a-, b- c- and d-MSH). POMC is mainly produced in the pituitary and its posttranslational processing occurs in a tissue-specific manner [1]. The proteolytic cleavage of POMC by prohormone convertase 1 (PC1) generates ACTH and b-lipotropin in the corticotrophs of the anterior pituitary, whereas cleavage by PC1 and PC2 produces a-MSH and b-endorphin in the melanotrophs of the pars intermedia [2]. The melanocortins exert its physiological role by binding to a family of specific G protein-coupled receptors (GPCR) that positively couple to adenylyl cyclase. Pufferfish have only 4 receptors with no melanocortin MC3R, while zebrafish (Danio rerio) has six MCRs, with MC3R and two copies of the melanocortin MC5R [3]
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