β-MSH (human)

A radioimmunoassay method for beta-melanocyte-stimulating hormone (beta-MSH) has been developed and utilized in the identification and quantification of this hormone in human plasma and tissues. The concentration of beta-MSH in two human pituitary glands was found to be approximately 350 mug/g. beta-MSH was identified in the tumor tissue of all 11 patients with the ectopic ACTH syndrome who were studied; concentrations in individual cases ranged from 3 to 1600 ng/g. In plasma of chronically hyperpigmented patients with Addison's disease, Cushing's disease (after bilateral adrenalectomy), and the ectopic ACTH syndrome, beta-MSH concentrations of 0.5-6 ng/ml were found. The degree of clinical hyperpigmentation was well correlated with the quantity of beta-MSH in the plasma. beta-MSH concentrations in the plasma of normal subjects were less than 0.09 ng/ml. In all of these circumstances, bioassays for MSH were also performed, and it was found that most of the biologic MSH activity of the plasma and tissues could be accounted for by beta-MSH.

Proopiomelanocortin (POMC) belongs to the opioid/orphanin gene family whose peptide precursors include either opioid (YGGF) or the orphanin/nociceptin core sequences (FGGF). In addition to POMC the family includes the proenkephalin (PENK), prodynorphin (PDYN), and nociceptin/proorphanin (PNOC) precursors. The opioid core sequence in POMC is incorporated by the β-endorphin that occupies the C-terminal region but this propeptide also exhibits at least two "alien" melanocortin core sequences (HFRW). An ACTH/MSH fragment merged into the opioid fragment not earlier than the two tetraploidizations of the vertebrate genome. Therefore, POMC exhibit a complex "evolutionary life" since the gene has coevolved together with two different receptor systems, i.e., opioid and melanocortin following a horse trading system. In this article, we summarize the different evolutionary hypotheses proposed for POMC evolution.

[NIe4,Asp5,d-Phe7,67Ga/68Ga-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid- Lys11]-α-MSH4-11(67Ga/68Ga-NAPamide) is a radioligand developed as a molecular imaging probe for primary and metastatic melanoma (1).67Ga/68Ga-NAPamide is an α-melanocyte-stimulating hormone (MSH) peptide labeled with67Ga or68Ga.67Ga is a gamma emitter with a physical half-life (t½) of 78.2 h and can be used for gamma imaging.68Ga is a positron emitter with a physicalt½of 68 min and is suitable for positron emission tomography (PET).Malignant melanoma is the sixth most common cancer in the United States (2). Early diagnosis and prompt surgical removal comprise the best approach for a possible cure (3). The melanocortin (MC) system is the best characterized neuropeptide network of the skin, and it is involved in pigmentation regulation, cortisol production, and many other physiological processes (4). Most cutaneous cell types express MC receptors, proopiomelanocortin (POMC), and prohormone convertases, and they also release MCs. Five MC receptors (MC-1 to MC-5) have been cloned and characterized as receptors that belong to the G-protein-coupled receptor superfamily. MSHs (α-, β-, and γ-MSH) are derived from POMC by the proteolytic action of prohormone convertases. α-MSH (Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2) is a peptide of 13 amino acids and is the most potent, naturally occurring, melanotropic peptide (5). The biological effects of α-MSH are mediatedviaMC receptors.Although PET imaging with [18F]fluoro-2-deoxy-2-d-glucose ([18F]FDG) is effective in the detection of melanoma, it is not melanoma-specific and some melanoma cells do not take up [18F]FDG (6, 7). Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC-1 receptors that are overexpressed on human and mouse melanoma cells (6, 8-11). Some studies have successfully used 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) coupled to the α-MSH peptide analogs for radiolabeling. These α-MSH derivatives (DOTA-α-MSH) can be labeled with a variety of radionuclides (6). Froidevaux et al. (12) reported the synthesis of111In-DOTA-[Nle4-d-Phe7]-α-MSH (111In-DOTA-NAP-MSH) and111In-[βAla3,Nle4,Asp5,d-Phe7,Lys10]-α-MSH3-10(111In-DOTA-MSHOCT) that exhibited high affinity for the MC-1 receptors in mice bearing B16F1 melanomas. To improve the tumor/kidney uptake ratio, the same group of researchers designed a short linear α-MSH analog, NAPamide, with a net charge of +1 and DOTA conjugated to the C-terminal lysine (1). They radiolabeled DOTA-NAPamide with either67Ga or68Ga as a potential molecular imaging probe to target melanoma.