The MRNA Expression Of Melanocortin 2 Receptor Accessory Protein In Human Adrenal Cortical Tumors

Objectives:Adrenocorticotropin,depending of its receptor,plays the important role in the proliferation,differentiation and steroidogenesis of adrenal cortex.The melanocortin 2 receptor accessory protein(MRAP) is required for trafficking of the ACTH-R(,also called melanocortin 2 receptor,MC2R) to the plasma membrane.Our previous study shows that ACTH-R may play a role in the development of adrenal cortical tumors.The aim of this study is to analyze MRAP mRNA expression of in human adrenalcortical tumors and normal adrenal cortex and gain an insight into the action of MRAP on the development of adrenocortical tumors.Methods:Total RNA was exracted from adrenal tissue of 7 normal human adrenal cortex,11 aldosterone-producing adenoma and 12 Cushing syndrome(7 cortisol-producing adenomas and 5 macronodular adrenal hyperplasia).Real time quantitative PCR was used to analyze the mRNA expression of MRAP/β-Actin in the same sample and compared among the different tissues.It was studied whether the mRNA expression of MRAP correlated with the tumor diameter,basal plasma aldosterone level,clinical manifestation and so on.Results:1.The ratio MRAP/β-Actin mRNA was 0.79±0.29 in normal adrenal cortex,and was 0.90±0.47 in aldosterone-producing adenoma.Compared with normal adrenal cortex, the difference was not significant(p＞0.05).The ratio MRAP/β-Actin mRNA was 0.32±0.30 in Cushing syndrome(cortisol-producing adenoma and macronodular adrenal hyperplasia),and it was much lower than normal adrenal cortex(p＜0.01).2.There was a significant difference in MRAP mRNA expression between aldosterone-producing adenoma and Cushing syndrome(cortisol-producing adenoma and macronodular adrenal hyperplasia)(p＜0.01),3.The difference in MRAP mRNA expression between cortisol-producing adenoma (0.23±0.09) and macronodular adrenal hyperplasia(0.45±0.44) was not significant (p＞0.05).4.In APA,the MRAP mRNA expression had a positive correlation with the plasma aldosterone level to upright stimulation(r=0.667,p=0.05) and a negative correlation with the plasma angiotensinⅡlevel to upright stimulation(r=-0.833,p=0.005),but had no correlation with tumor diameter and basal plasma aldosterone level(p＞0.05).Conclusions:1.the MRAP mRNA expression is not the same in different adrenocortical tumors.It is lower in cortisol-producing adenoma and macronodular adrenal hyperplasia than in aldosterone-producing adenoma and normal adrenal cortex.2.In APA,the MRAP mRNA expression had a positive correlation with the plasma aldosterone level to upright stimulation and a negative correlation with the plasma angiotensinⅡlevel to upright stimulation.It is suggested that MRAP could effect the regulation of ACTH to aldosterone via ACTH-R.