Expression of adrenomedullin and its receptors in the human adrenal cortex and aldosteronomas

Adrenomedullin (ADM) is a hypotensive peptide, that derives from the proteolytic cleavage of pro(p)ADM and acts through at least two subtypes of receptors, called L1-receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR may function as a calcitonin gene-related peptide (CGRP) or a selective ADM receptor depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of proteins, referred to as receptor-activity-modifying proteins (RAMPs). Although adrenal cortex is known to be one of the main target organs of ADM, its expression of the ADM and its receptor has not yet been extensively investigated. Reverse transcription (RT)-polymerase chain reaction (PCR) revealed the expression of the pADM and peptidyl-glycine alpha-amidating monooxigenase (PAM) genes in four human adrenal cortexes and four aldosteronomas. Since PAM is the enzyme that converts immature ADM to the mature and active form, these findings suggest that the two tissues are able to produce ADM. RT-PCR also demonstrated high levels of L1-R mRNA and relatively low levels of CRLR mRNA, as well as the presence of specific mRNAs for the three RAMPs, thereby indicating that human adrenal cortex and aldosteronomas are provided with the two subtypes of classic ADM receptors. In conclusion, our investigation provides the first evidence that human adrenal cortex and aldosteronomas express the ADM system, that may play a role in the paracrine or autocrine control of their functions.