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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
12:37

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Published on: September 7, 2013

Fish melanocortin system.

José Miguel Cerdá-Reverter1, Maria Josep Agulleiro, Raúl Guillot R

  • 1Department of Fish Physiology and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS), Consejo Superior de Investigaciones Científicas (CSIC), Castellón, Spain. cerdarev@iats.csic.es

European Journal of Pharmacology
|January 7, 2011
PubMed
Summary

Melanocortin receptors (MC) and their ligands regulate pigmentation and energy balance. Fish exhibit diverse MC receptor numbers, with ASP and AGRP influencing these processes.

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Area of Science:

  • * Comparative genomics and molecular endocrinology.
  • * Focus on G protein-coupled receptors and signalling pathways.

Background:

  • * Melanocortin (MC) signalling involves MC receptors binding to melanocyte-stimulating hormones (MSHs).
  • * Tetrapods possess five MC receptors (MC1-MC5), while fish display variations, e.g., zebrafish have six, pufferfish have four.
  • * Agouti-signalling protein (ASP) and Agouti-related peptide (AGRP) are key modulators.

Purpose of the Study:

  • * To explore the diversity and function of melanocortin system components in fish.
  • * To investigate the roles of ASP and AGRP in fish physiology.
  • * To understand the regulation of pigmentation and energy balance via melanocortin signalling.

Main Methods:

  • * Comparative analysis of fish genomes for melanocortin receptor and ligand genes.
  • * In vitro expression studies of sea bass MC1 and MC4 receptors.
  • * Investigating the function of ASP and AGRP as inverse agonists.
  • * Overexpression studies of AGRP and ASP transgenes in zebrafish.

Main Results:

  • * Fish exhibit diverse melanocortin receptor repertoires, including multiple MC5 receptor copies in some species.
  • * Agouti-signalling protein (ASP) is expressed in skin, while Agouti-related peptide (AGRP) is hypothalamic.
  • * Fish MC2 receptor requires accessory proteins (MRAP) for function; other MC receptors bind MSHs.
  • * α-MSH and MC1 receptor interaction is crucial for pigmentation; mutations reduce melanization.
  • * Central MC4 and MC5 receptors regulate feeding behaviour and energy balance.
  • * Peripheral MC2 and MC5 receptors influence lipid metabolism.
  • * Sea bass MC1 and MC4 receptors are constitutively active; ASP and AGRP act as inverse agonists.
  • * AGRP and ASP transgene overexpression induce obesity and reduced melanization in zebrafish.

Conclusions:

  • * The melanocortin system is highly conserved but shows significant evolutionary divergence in fish.
  • * Melanocortin signalling plays critical roles in pigmentation, energy homeostasis, and lipid metabolism across vertebrates.
  • * ASP and AGRP are potent regulators of these physiological processes in fish, with implications for understanding obesity and pigmentation disorders.