Stimulation of β 2-adrenergic receptors results in smooth muscle relaxation in tissues such as the uterus, bronchi, and skeletal muscle arterioles. Stimulation of β 1-adrenergic receptors in the myocardium results in increased heart rate and contractility. α-Adrenergic receptors display greater affinity for norepinephrine compared with epinephrine, and the opposite is true for β-adrenergic receptors. Target tissue responses are mediated by α- and β-adrenergic receptors. Basal levels of adrenal catecholamine secretion are normally low, although large (up to 50-fold) increases in levels may be observed in response to major physiologic or psychological stressors. Sympathetic stimulation of the adrenal medulla results in the release of stored catecholamines into the circulation. Epinephrine is created by the action of PNMT, which, unlike the other enzymes involved in catecholamine synthesis, is localized to the chromaffin cells of the adrenal medulla and organ of Zuckerkandl. Decarboxylation of L-dopa generates dopamine, which is then β-hydroxylated to form norepinephrine. Synthesis of catecholamines in the adrenal medulla begins with the hydroxylation of tyrosine, a rate-limiting step that generates dihydroxyphenylalanine ( L-dopa) in the cytosol (Fig. 1, 2Ĭatecholamine Biosynthesis and Physiology Roger Guillemin, Andrew Schally, and Rosalyn Yalow were awarded the Nobel Prize in Physiology or Medicine in 1977 for characterizing the peptide hormones of the brain that underlie the HPA axis as we now understand it. The Austrian-born endocrinologist Hans Selye first described the stress response in mammals in 1936 and made major contributions to the understanding of the hypothalamic-pituitary-adrenal (HPA) axis. Edward Kendall, Tadeus Reichstein, and Philip Hench jointly received the 1950 Nobel Prize in Physiology or Medicine for their groundbreaking work on the adrenocortical hormones. Steroid hormones were crystallized from cortical extract (cortin) by Swiss and American investigators in the 1930s, but their highly similar chemical structures made isolation of the individual compounds challenging. Adrenaline (or epinephrine) was first isolated from adrenal extract at the turn of the century. Although Thomas Addison described the clinical features of primary adrenal failure in 1855, it was not until almost a century later that the adrenal hormones were fully isolated and characterized. The German comparative anatomist Albert von Kölliker (1817-1905), who noted the presence of the adrenals in a number of vertebrate species, is credited with first identifying two distinct portions of the adrenal gland, the cortex and the medulla. The adrenal glands were first described by the Italian anatomist Bartolomeo Eustachi in 1563.
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