Biological actions of melanocyte-stimulating hormone.

Melanocyte-stimulating hormone (alpha-melanotropin, MSH) may function in a number of diverse physiological roles. MSH stimulates (1) rapid translocation of melanosomes (melanin granules) in dermal melanophores to effect rapid colour change and (2) melanogenesis in normal and abnormal (melanoma) epidermal melanocytes. Both actions involve (1) initial binding of the peptide on the melanocyte membrane, (2) transduction of signal to adenylate cyclase, and (3) increased cytosolic levels of cyclic AMP. Efforts to prepare radioiodinated MSH and analogues for radioreceptor studies using melanoma membranes and intact cells reveal that conventional iodination procedures inactivate the hormone because of oxidative and iodination effects on specific structural components of the peptide. These effects can be circumvented by the use of synthetically tailored MSH analogues. Transduction of signal from receptor to adenylate cyclase requires calcium, but prostaglandin or beta-adrenoceptor stimulation of melanophores does not. The nucleotide and metal ion requirements for mouse melanoma adenylate cyclase activity have been characterized. There is both a transcriptional and translational requirement for MSH stimulation of tyrosinase activity and melanin production in melanoma cells. Melanosome translocation within melanophores is enhanced in the absence of extracellular calcium. A model for the MSH control of melanosome movements suggests a bifunctional, but compartmentalized, role for calcium in the action of MSH.