Neural melanocortin receptors are differentially expressed and regulated by stress in rat hypothalamic-pituitary-adrenal axis.

Genetic knockout and null mutations of melanocortin system components lead to phenotypes that recapitulate the metabolic syndrome such as obesity, hypertension and insulin resistance. Since stress is known to modify metabolic and cardiovascular function, we hypothesized the involvement of the neural melanocortin system in the stress response. Male rats were subjected to rapid-eye-movement sleep deprivation stress and the levels of proopiomelanocortin (POMC), MC3R, MC4R and MC5R transcripts in the hypothalamic-pituitary-adrenal axis (HPA) determined by real-time PCR. Increased levels of POMC transcripts were observed in the hypothalamus and adrenal gland tissues but there were no significant changes in the expression of the receptors genes. Whereas MC3R and MC5R are expressed in all HPA tissues, MC4R seems to be restricted mainly to the hypothalamus. It is possible that melanocortin receptors function in different aspects of the neuron. In vitro studies showed similar cellular distribution patterns for MC3R and MC4R and sequence analyses revealed strong conservation of the putative G-protein coupled receptors (GPCR) C-terminal membrane localization signal, EX(3-7)II/L motif, in MC3R, MC4R and MC5R. These data suggest that the physiological roles of neural melanocortin receptors, MC3R and MC4R, are likely determined by distinct tissue distribution patterns and suggest a role for hypothalamic and intra-adrenal melanocortin systems in the manifestation of stress related pathologies.