The role of adrenomedullin as a growth regulatory peptide in the normal and malignant setting

Abstract

Adrenomedullin (AM ) is a recently discovered pluripo1ent peptide initially isolated fraro a human adrenal gland tumor (pheochromocytoma). Adrenomedullin has been shown to have an ancient origin with immunoreactive species fOWld in maromals, birds, reptiles, amphibians, fish , and eemnoderms (s t a r fish ). Given its highly conserved evolutionary expression, AM is thought te playa critica! !•ole in spedes survival. This peptide has been show lo mediate a variety of physiological fu netlons, of which iis involvement in growth r egulation wil1 be tbe central focus of this papero In the following text, we will review the cited Iiterature in this area and inelude our own observations regarding AM express10n in carcinogenesis, embryogenesis, and wound r epair. Adrenomedullin will be shown to induce both growth promotian or growth suppression depending on the taTget cell examined aud the sUITounding nutritional environment in which the analysis was done. Its implied role as a mitogen, aogiogenic fador, and apoplosis survival factor will be critiqued and evaluated relative to its impor tance in the cel! proHferation process. Finally, we will review the a ntimicrobiaJ effect AM has on severa1 human pathogens ( Es•cherichia coli and Candidn albi.cans) and demonstrate its partieipation in the host immune response syslem as a first line defense peptide.