Eugene J. Barrett
The human adrenal glands, each weighing only ~4 g, are located above the upper pole of each kidney in the retroperitoneal space. They produce four principal hormones: cortisol, aldosterone, epinephrine (adrenaline), and norepinephrine. Each adrenal gland is composed of an inner medulla and an outer cortex (Fig. 50-1). Embryologically, the cortex is derived from mesoderm, whereas the medulla is derived from neural crest cells (see p. 261) that migrate into the developing cortex. The cortex produces two principal steroid hormones, cortisol and aldosterone, as well as several androgenic steroids. The medulla produces epinephrine and norepinephrine.
FIGURE 50-1 Anatomy of the adrenal gland. An adrenal gland—actually two glands, cortex and medulla—sits upon each kidney. The adrenal cortex comprises three layers that surround the medulla: glomerulosa, fasciculata, and reticularis. The blood supply enters the cortex in the subcapsular region and flows through anastomotic capillary beds while coursing through first the cortex and then the medulla. The adrenal medulla contains chromaffin cells.
The adrenal cortex can be further divided into three cellular layers: the glomerulosa layer near the surface, the fasciculata layer in the midcortex, and the reticularis layer near the cortical-medullary junction. Aldosterone, the main mineralocorticoid in humans, is made in the glomerulosa cell layer. Cortisol, the principal glucocorticoid, is made in the fasciculata and to a small extent in the reticularis layer. The adrenal androgens—dehydroepiandrosterone (DHEA) and its sulfated form DHEAS—are made in the reticularis layer. Although both cortisol and aldosterone are made by enzymatic modification of cholesterol and are structurally quite similar, their actions on the body differ dramatically. Cortisol is considered a glucocorticoid because it was recognized early on to increase plasma glucose levels; deficiency of cortisol can result in hypoglycemia. Aldosterone is considered a mineralocorticoid because it promotes salt and water retention by the kidney. The activities of these two hormones overlap, particularly at high hormone levels, but this distinction is still very useful in identifying their most obvious functions. DHEA and DHEAS are weak androgens (compared to testosterone or dihydrotestosterone) and little is known about the regulation of their secretion. Plasma DHEA concentrations follow a diurnal pattern like that of cortisol. DHEAS circulates at much higher concentrations and shows no diurnal fluctuation.
In the adrenal medulla, chromaffin cells produce epinephrine (or adrenaline), a catecholamine that is synthesized from the amino acid tyrosine. Although the primary product of the medulla is epinephrine, it also produces variable amounts of the epinephrine precursor norepinephrine. These catecholamines are distinct from the steroid hormones both structurally and functionally.