?-MSH and Desacetyl-?-MSH Signaling through Melanocortin Receptors
The functional significance of N-terminal acetylation of ACTH[113]NH2 is unknown. N-terminal acetylation of ACTH[113]NH2 (known as desacetyl-?-MSH) to produce ?-MSH enhances some activities of ACTH[113]NH2 and virtually eliminates others. To determine whether ?-MSH and desacetyl-?-MSH diverge in their coupling to melanocortin receptors in vitro, we measured the sensitivity of MC1, MC3, MC4, and MC5 receptors stably expressed in HEK293 cells to these peptides, functionally coupling them to adenylyl cyclase and a calcium signaling pathway. ?-MSH and desacetyl-?-MSH similarly coupled these overexpressed receptors to both signaling pathways. In contrast, we discovered that ?-MSH significantly increased primary rat osteoblast proliferation while for desacetyl-?-MSH there was only a trend to do the same. Osteoblast cells expressing very low levels of endogenous melanocortin receptors, in contrast with transfected HEK293 cells overexpressing a single melanocortin receptor, may provide an in vitro model for differentiating between ?-MSH and desacetyl-?-MSH signaling.
?-msh desacetyl-?-msh signaling melanocortin receptor osteoblast