Endocrine Abstracts

Melanocortin receptor accessory protein (MRAP) is a single transmembrane domain protein, which has been identified as essential for the cell surface trafficking and signalling of the ACTH receptor (melanocortin 2 receptor (MC2R)). MRAP is essential for the function of MC2R, but regulation of its expression remains unclear. This study aims to identify factors regulating MRAP gene expression and whether these factors would affect the signalling of MC2R.

The mouse adrenal cell line (Y1) was stimulated with a range of hormones/stimulants for 4 h and MRAP mRNA expression was quantified using real time RT-PCR.

There was a four-fold increase in MRAP expression following stimulation with adrenocorticotropic hormone (ACTH) (10⁻⁷ M) and forskolin (10⁻⁵ M); whilst dexamethasone (10⁻⁶ M) induced a two-fold increase. Time course studies showed that the peak expression of MRAP was after 2 h stimulation with ACTH. Forskolin caused a gradual increase in MRAP expression, reaching its peak around 6 h, while dexamethasone caused maximal effect after 4 h. MC2 receptor function studies showed that treatment of cells with ACTH resulted in a lower cAMP response after 4 h, therefore it can be said that ACTH desensitises this receptor. In comparison the other agents do not effect the sensitisation of MC2R.

This study has shown that MRAP expression can be up-regulated by ACTH, forskolin and to a lesser extent dexamethasone. Activation of the MC2R by ACTH leads to cAMP signaling and positive regulation of its expression. This contrasts with the regulation of the MC2R, which in previous studies has been found to be modest. Thus it seems likely that regulation of MRAP gene expression is one mechanism by which the ACTH receptor complex is controlled. Further studies will address the protein expression of MRAP and its effect on signalling of MC2R in response to ACTH.