1. Human beta-melanocyte-stimulating hormone revisited
X Bertagna, F Lenne, D Comar, J F Massias, H Wajcman, V Baudin, J P Luton, F Girard Proc Natl Acad Sci U S A. 1986 Dec;83(24):9719-23. doi: 10.1073/pnas.83.24.9719.
It is generally accepted that human beta-melanocyte-stimulating hormone (h beta MSH) does not normally exist in humans but was merely an artifactually generated 22-amino acid peptide corresponding to a lipotropin (LPH) fragment (residues 35-56). We examined whether the shorter 18-amino acid peptide h beta MSH-(5-22) could be detected in some human tissues. Normal human pituitaries and hypothalami as well as corticotropin-secreting pituitary and nonpituitary tumors were extracted and chromatographed on Sephadex G-50, and the fractions were measured with two radioimmunoassays using either a COOH-terminal human gamma LPH (h gamma LPH) antiserum that recognized equally h gamma LPH, h beta MSH, and h beta MSH-(5-22) or a mid-portion h gamma LPH antiserum that recognized h gamma LPH and h beta MSH but not h beta MSH-(5-22). Normal pituitaries and pituitary tumors contained a single immunoreactive material coeluting with h gamma LPH. The hypothalami and the nonpituitary tumors all contained h gamma LPH and a smaller molecular weight material that was only detected in the COOH-terminal h gamma LPH radioimmunoassay; its elution volume (Ve/V, 0.75) was identical to that of h beta MSH-(5-22) but different from that of h beta MSH (Ve/V, 0.60); on reversed-phase HPLC, it coeluted with synthetic h beta MSH-(5-22) with a retention time different from that of h beta MSH. It is concluded that h beta MSH-(5-22) that corresponds to the 18-amino acid peptide h beta LPH-(39-56), flanked by two pairs of basic amino acids within the h beta LPH molecule, is a normal maturation product of proopiomelanocortin in human nonpituitary tissues.
2. Melanocyte-stimulating hormone: a regulator of human melanocyte physiology
G Hunt Pathobiology. 1995;63(1):12-21. doi: 10.1159/000163930.
Although the melanocyte-stimulating hormone (MSH) is well-recognised as a pigmentary hormone in animals, its role in human pigmentation is still a matter for conjecture, not least because cultured human melanocytes have proved to be relatively refractory to the peptide. However, recent work has shown that human melanocytes can respond to MSH peptides and the related adrenocorticotropic hormone. While the pigmentary responses are the most studied, they are by no means the only effects of these peptides on human melanocytes. This article reviews recent work on the responses of human melanocytes to MSH peptides and demonstrates that these peptides may be key regulators of human melanocyte physiology.
3. The melanocortin-1 receptor and human pigmentation
Z Abdel-Malek, I Suzuki, A Tada, S Im, C Akcali Ann N Y Acad Sci. 1999 Oct 20;885:117-33. doi: 10.1111/j.1749-6632.1999.tb08669.x.
alpha-Melanocyte stimulating hormone (alpha-MSH) is known to be the main physiologic regulator for integumental pigmentation of various vertebrate species. However, the role of alpha-MSH and related melanocortins in the regulation of human cutaneous pigmentation is only beginning to be understood. Cloning of the melanocortin-1 receptor (MC1R), and the feasibility of establishing normal human epidermal melanocyte cultures have made it possible to demonstrate direct and specific biological effects of alpha-MSH on these cells. It is now recognized that both alpha-MSH and ACTH have similar mitogenic and melanogenic effects on human epidermal melanocytes. These effects are mediated by binding of these hormones to the specific MC1R that recognizes them both with similar affinity. Human MC1R is homologous to its mouse counterpart in that its activation leads to stimulation of eumelanin synthesis. MC1R is also the binding site for agouti signaling protein (ASP), the product of the agouti locus. Human epidermal melanocytes respond to purified recombinant mouse or human ASP, with a reduction in basal tyrosinase activity, and complete abrogation of the mitogenic and melanogenic effects of alpha-MSH. These results suggest that ASP induces pheomelanin synthesis by competing with alpha-MSH for binding to the MC1R. This receptor seems to be subject to regulation by a variety of paracrine and/or autocrine factors that are synthesized in response to exposure of the skin to ultraviolet radiation (UVR). Activation of MC1R seems to be pivotal for UV-induced melanogenesis, since stimulation of the cAMP pathway plays a key role in the melanogenic response of human epidermal melanocytes. The melanogenic response to UVR might be influenced by the presence of allelic variants of the MC1R gene. Allelic variants have been identified and shown to be associated with red hair, poor tanning ability, and possibly melanoma. The possible influence of these variants on the function of the MC1R needs to be investigated, in order to understand the physiological consequence of these mutations. Also, the interaction of alpha-MSH with other factors that are known to affect pigmentation needs to be better understood in order to define the role possible of this hormone and its receptor in acquired human cutaneous hyper- or hypopigmentation.
