Molecular genetics of the ACTH and melanocyte-stimulating hormone receptors.

ABSTRACT

The related ACTH and melanocyte-stimulating hormone (MSH) receptors control adrenal steroidogenesis and pigmentation in response to an overlapping set of peptides derived from the proopiomelanocortin (POMC) molecule. The recent cloning of these receptors has already opened up a new understanding of their role in normal and pathologic functioning of the adrenal cortex, and of the process of pigmentation. The murine MSH receptor maps to a genetic locus called extension, a locus known since early in this century to control the relative amounts of the two major types of melanins eumelanin and phaeomelanin. The highly variable pigmentation phenotypes resulting from different extension locus alleles are caused by structural mutations in the MSH receptor that alter the degree of its signal-transducing capacity. A mutation in the ACTH receptor in a patient with ACTH resistance has also recently been reported. It is likely that the etiology of this rare disease includes mutations that affect the functioning of the ACTH receptor.