Background: The melanocortin 2 receptor (MC2R)/melanocortin 2 receptor accessory protein (MRAP) are critical components of the hypothalamo-pituitary-adrenal axis (HPA). MRAP2, homologue of MRAP, can also regulate the MC2R in vitro, however, the physiological significance of this is unclear. We studied the expression of the MRAPs and MC2R in a well-defined rat model of endotoxin induced septic shock. These animals have been shown to have higher ACTH and corticosterone levels.
Materials and Methods: Rats (n=68 per group) were either untreated or treated with intraperitoneal (IP) saline or lipopolysaccharide (500 ug/kg). Adrenal cortical tissue was extracted and MRAP, MRAP2 and MC2R expression was quantified by real-time RT-PCR.
Results: MRAP expression was significantly higher in animals treated with 500 ug/kg LPS compared to baseline or saline treated (P<0.0001). In comparison, there was no significant change in MC2R or MRAP2 expression between the groups.
Conclusions: Activation of the HPA axis seen in LPS induced septic animals was associated with a significant increase in adrenal MRAP expression whilst MC2R was unchanged. This may represent the preferential production and usage of a small accessory protein which has the ability to traffic an endogenous pool of MC2R within the adrenal cortical cells. Interestingly, there is no change in MRAP2 expression suggesting that it may not play an important role in corticosterone production in adult septic animals.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: RJG is supported by a Wellcome Clinical Research Training Fellowship (grant number WT092024MA). LFC holds an MRC/Academy of Medical Sciences Clinician Scientist Fellowship (grant number G0802796).