Adrenomedullin from a pheochromocytoma to the eye: implications of the adrenomedullin research for endocrinology in the 21st century.

In the last several decades, the concept of "endocrinology" has been greatly changed. One major change was due to the discovery of peptide hormones secreted by the organs that were not "classical" endocrine organs. For example, corticotropin-releasing hormone and many neuropeptides are secreted by the neurons, atrial natriuretic peptide by the heart, endothelin-1 by the vascular endothelial cells, and leptin by the adipose tissues. Now, the brain, heart, vascular tissue and adipose tissue can be considered to be endocrine organs. Cardiovascular diseases and obesity are therefore important targets of the endocrine research. Adrenomedullin is a potent vasodilator peptide consisting of 52 amino acids. It was originally discovered from a human pheochromocytoma, and belongs to the calcitonin gene-related peptide (CGRP) family. Adrenomedullin is produced and secreted by various types of cells, for example, vascular endothelial and smooth muscle cells, cardiomyocytes, fibroblasts, macrophages, neurons, glial cells, and retinal pigment epithelial cells. Such ubiquitous expression has not been observed in other neuropeptides, including neuropeptide Y and CGRP. Expression of adrenomedullin is induced by hypoxia and proinflammatory cytokines. In addition to vasodilator actions, this peptide has central inhibitory actions on water drinking and salt appetite, effects on the secretion of some hormones and cytokines, inotropic actions and effects on cell growth and apoptosis. Adrenomedullin is produced by various non-endocrine tumors, as well as endocrine tumors, and acts as a growth stimulatory factor for the tumor cells. Adrenomedullin seems to be involved in the pathophysiology of many diseases, including ischemic heart diseases, inflammatory diseases, tumors, and even eye diseases. The adrenomedullin research implies that "the neuroendocrine system" exists in much broader types of cells than previously thought, and that the endocrine research is able to contribute to the understanding of the pathophysiology of many diseases.