The five melanocortin receptors (MC1-5) are G-protein-coupled receptors (GPCRs), expressed in the central nervous system and peripheral tissues, which are activated by melanocyte-stimulating/adrenocorticotrophic hormones and modified by melanocortin receptor accessory proteins (MRAP1 and 2). MCs have well-characterised roles in the regulation of appetite, immune and stress responses, but their expression in a range of tissues suggests they may have other roles in modifying physiology. We have characterised MC and MRAP expression in the female murine pituitary and found expression of MCs 3, 4 and 5, as well as MRAP1 and 2, that differentially change with age. This suggests that MC expression may mediate coordination of pituitary gland axes and as well as underlying alterations in pituitary gland functional output across lifespan. Further analysis with highly specific chromogenic RNA in situ ybridisation (RNAscope®) shows that a proportion of
somatotroph cells co-express MC3, consistent with our previous studies showing that loss of this receptor leads to alterations in the GH axis.
Since it is becoming apparent that interactions of MCs and MRAPs with other GPCRs can modify signalling, we are testing the effects of their co-expression with established receptors regulating the GH axis both in the presence and absence of MC ligands. GPCR function is being tested both by directly monitoring specific GPCR activation and their down-stream signalling pathways. These studies will have implications for fundamental understanding of pituitary axes crosstalk, as well as potential off-target effects of pharmacological