Cloning of the Melanocortin Receptors

  • Kathleen G. Mountjoy
Part of the The Receptors book series (REC)


Melanocortin peptides (adrenocorticotropin [ACTH], α-, β-, and γ-melanocyte stimulating hormone [MSH], and fragments thereof) derived from proopiomelanocortin (POMC) have a diverse array of biologic activities, many of which have yet to be fully elucidated. POMC, produced most abundantly in the pituitary, is also produced in the brain, in the neurons of the arcuate nucleus of the hypothalamus, and the commis sural nucleus of the solitary tract of the brainstem; it has also been detected in several peripheral tissues including skin, pancreas, and testis. POMC is differentially processed in the different pituitary lobes, and the processing in the brain differs from that in the pituitary. In the corticotropic cells of the anterior lobe of the pituitary, the major end product is the 39 amino acid, ACTH[1–39]. In the melanotrophs of the intermediate lobe of the pituitary, ACTH[l–39] is the precursor of α-MSH (ACTH[ 1–13]) and corticotropinlike intermediate lobe peptide (CLIP) (ACTH[18–391). The major fraction of α-MSH produced by pituitary melanotrophs is acetylated at the amino terminus, while most of brain-derived α-MSH is desacetylated. α, β, γl, γ2, and γ3-MSH peptides are processed from different regions of the POMC precursor to yield peptides sharing a conserved core of seven amino acid residues. Adult humans lack an intermediate lobe of the pituitary and thus have very little α-MSH in the serum. ACTH[ 1–39] is the predominant circulating melanocortin peptide in man while α-MSH is the predominant circulating melanocortin in most other species. γ-MSH peptides have been reported to be present in human skin, are detectable in human adult blood and γ3-MSH is increased in the circulation in patients with cardiac arrest, in sheep blood in response to acute hemorrhagic stress, and is also increased toward the end of gestation. The primary roles of MSH and ACTH are the regulation of pigmentation and adrenal corticosteroid synthesis, respectively. While α-and β-MSH have melanotropic activity, γ-MSH peptides have little, if any, activity when tested in mouse and hamster melanoma cells. ACTH also stimulates proliferation of the adrenal cortex and is crucial for the normal development of this tissue. Numerous other activities for the melanocortin peptides have been demonstrated in the central and peripheral nervous systems, in the immune system, on lipolysis, on pituitary function, parturition, and neuromuscular function. Since the 1950s, a number of biologic responses have been seen on intracerebroventricular introduction of these peptides (1). For example, central administration of melanocortin peptides has been reported to have effects on autonomic controls such as thermoregulation, food intake, cardiovascular function, behavior, and neuroendocrine homeostasis. Retention of learned behaviors, and recovery from nerve damage has also been reported. In addition to their effects on brain, melanocortin peptides exert a neurotrophic action on damaged peripheral nerve tissue (2). ACTH and α-MSH also have antipyretic activity following peripheral or intracerebroventricular administration (3).


Adrenal Cortex Polymerase Chain Reaction Fragment Intracellular Loop Melanocortin Receptor ACTH Receptor 
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  • Kathleen G. Mountjoy

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