Programmed Cell Death Mechanisms and Pheocromocytomas: Recent Advances in PC12 Cells

1.1 The adrenal medulla and its hormones There are two adrenal glands in our body that produce a number of vital hormones essential for survival. The adrenal glands, located at the superior poles of the two kidneys, are composed of two distinct layers, the adrenal cortex and the adrenal medulla. The outer adrenal cortex, which develops from the abdominal mesothelium, surrounding the medulla during embryogenesis, synthesizes and secretes the adrenocortical hormones, the mineralocorticoids and glucocorticoids, as well as the adrenogenic (sexual) hormones. The adrenal medulla, which comprises the central 20% of the gland, originates from the neural crest, and does not become distinct and compact until the adrenal cortex atrophies during the first few weeks postnatally. The adrenal medulla is a modified sympathetic ganglion which secretes in the bloodstream the catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) in response to sympathetic neural stimulation to the medullae. Depending on the physiological conditions, this secretion averages 80% epinephrine to 20% norepinephrine. Although dopamine is present in the adrenal and serves as a precursor for norepinephrine and epinephrine, minimal dopamine secretion occurs and the role of adrenal dopamine is not well understood. Cells of the medulla are known as pheochromocytes or chromaffin cells, referring to the dark color produced by the polymerization of oxidized catecholamines when these cells are exposed to chromium salts. The early medulla also contains neuroblasts and developing sympathetic ganglion cells, but these populations decrease with proliferation and maturation of the chromaffin cell population during the first years of life in the human. The pheochromocytes are arranged in nests and cords and contain abundant membrane-bound dense granules, in which the catecholamines are stored. On stimulation, these granules are transported to the cell surface via the microtubular system, and the neurotransmitter