The Role of the Melanocortin 3 Receptor in Mediating the Effects of Gamma‐MSH Peptides on the Adrenal

The pro‐opiomelanocortin (POMC)‐derived peptides, pro‐γ‐MSH (16K fragment), and Lys‐γ3‐MSH, have been shown to potentiate the steroidogenic action of corticotrophin (ACTH) on the adrenal cortex. Using a continuously perfused adrenal cell column system, we have tested the hypothesis that γ‐MSH peptides exert their effect through the Melanocortin 3 Receptor (MC3‐R), since this is the only known receptor to have high affinity for γ‐MSH peptides and has been suggested to be expressed in the rat adrenal. To investigate this hypothesis we tested whether the MC3‐R agonist MTII and antagonist SHU9119 could mimic or block the actions of pro‐γ‐MSH. We found that MTII could not mimic, and SHU9119 could not block pro‐γ‐MSH mediated potentiation of ACTH‐induced steroidogenesis. These results suggest that the MC3–R is not involved in mediating the potentiation effect, adding further evidence to the argument that another melanocortin receptor exists.