Endocrine Abstracts (2004) 7 P149

Investigating the potential role of melanocortin receptor 5 in the rodent adrenal gland

O Kosti1, D Renshaw1, J Harrold2, R Cone3 & J Hinson1

1Department of Molecular Endocrinology, Barts and the London, London, UK; 2Department of Medicine, University of Liverpool, UK; 3Vollum Institute, Portland, USA.

Two members of the melanocortin (MC) receptor family are abundantly expressed in the adrenal cortex, namely MC2R and MC5R. MC2R binds only ACTH and is known as the ACTH receptor, the role of MC5R however is still under investigation. It is known that alpha-MSH stimulates aldosterone secretion by the rat adrenal cortex, by an MC2R-independent mechanism, although the receptor involved has not been identified. The experiments were designed to investigate the role of MC5R in the adrenal cortex.

125I-NDP-alpha-MSH binds all members of the melanocortin receptor family except MC2R. Autoradiography experiments using 125I-NDP-alpha-MSH showed that in the case of chronic aldosterone stimulation achieved by 3 week dietary sodium depletion, a significant increase in binding sites occurred in frozen rat adrenal sections. Moreover, in our attempt to quantitatively study melanocortin receptor expression after sodium depletion in rat adrenals using real-time PCR methods, a clear positive correlation between plasma aldosterone levels and MC2R and MC5R was observed among sodium deplete animals. These data suggest that MC5R gene expression is up-regulated by sodium depletion. The role of MC5R was further investigated using the MC5R knockout (KO) model. Unfortunately, in this particular strain of mice, neither Wild-Type (WT) nor KO mice responded to alpha-MSH stimulation, however an enhanced ACTH response was seen in KOs compared to WTs. This corresponded to a 5-fold increase in MC2R gene expression. It is still unclear whether MC5R mediates the effects of a-MSH within the rodent adrenal gland.

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