Adrenomedullin: A Novel Peptide Requires Coordination Of Genetic, Physiologic And Environmental Factors

A healthy pregnancy requires strict coordination of genetic, physiologic, and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Adrenomedullin (ADM) is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide (CGRP) initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla, endothelial and vascular smooth muscle cells, myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor (CRLR), a member of serpentine receptor superfamily, and receptor activity modifying protein (RAMP) type 2 or 3. ADM has also some affinity for CGRP receptor composed of CRLR and RAMP1. Supported by mechanistic studies in genetic animal models, there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With measurement of foetal resorption sites, we can examine the importance of adrenomedullin, a peptide hormone in pregnancy which alters due to genetic, physiologic and environmental factors. A growing body of evidence illustrates AM as a pivotal component in normal physiology and disease with marked beneficial effects in the host defense mechanism.