Receptors for Melanocortin Peptides in the Hypothalamic‐Pituitary‐Adrenal Axis and Skin

The syndromes of hereditary IGD and triple A syndrome are potentially life threatening and severely disabling diseases. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The defects in the ACTH receptor causing IGD help illuminate the mechanisms of ligand binding and signal transduction by this receptor. Identification of the molecular defect(s) responsible for IGD cases with a normal ACTH receptor structural gene and for the triple A syndrome remains a challenge, which will hopefully eventually provide further insight into the mechanisms of adrenocortical function. The cloning of the melanocortin receptors has been a giant step towards a better insight into the physiological role of the POMC-derived peptides. It is now becoming apparent that the differential processing of POMC in the brain, the pituitary, and peripheral tissues, yielding a number of different biologically active melanocortin peptides, combined with the distinct tissue distribution and pharmacological profile of the melanocortin receptors will help elucidate the molecular basis of these functions.