MSH receptors in immortalized human epidermal keratinocytes: a potential mechanism for coordinate regulation of the epidermal-melanin unit.

Receptors for melanotropin (MSH) were found to be expressed by immortalized primary human epidermal keratinocytes (RHEK-1). Using 125I-beta MSH as a probe, the MSH receptors from mouse melanoma cells and human keratinocytes were found to be remarkably similar. In each cell line, there were high and low affinity receptors, with the high affinity classes showing positive cooperativity. Competition of 125I-beta MSH for binding with non-radioactive MSH revealed similar profiles. Cross-linking studies, followed by gel electrophoresis and autoradiography, showed almost identical gel migration patterns. Both cell types expressed internal as well as plasma membrane binding sites. MSH receptors on both cell types were up-regulated by ultraviolet light and by MSH itself. Although the function of MSH receptors expressed by the immortalized keratinocytes is unknown, the results are consistent with recent reports that proliferation of epidermal keratinocytes is stimulated by MSH and that proopiomelanocortin genes are expressed in the epidermis. These results support a model in which keratinocytes and melanocytes, interacting in an "epidermal-melanin unit," each respond to UV light signals with increased MSH receptor activity.