The adrenal glands, paired structures located retroperitoneally at the upper pole of each kidney, include two distinct endocrine organs: an outer cortex that secretes steroid hormones and an inner medulla that, as part of the sympathetic nervous system, secretes catechol amines (epinephrine and norepinephrine). The cortex consists of three zones: the outer zona glomerulosa, which secretes a potent mineralocorticoid hormone, and the inner zonae fasciculata and reticularis, which secrete glucocorticoids, androgens and minute quantities of estrogens. Each of these steroid hormones as well as the catechol amines causes striking effects when produced in excess. In contrast, only glucocorticoid and mineralocorticoid hormones, which are secreted exclusively by the adrenal gland, are physiologically important products. The gonadal production of androgens in men and estrogens in women and the secretion of norepinephrine by sympathetic ganglia are quantitatively more important source of these hormones and neurotransmitters.
Major Hormones of the Adrenal Gland
Cortisol is the major glucocorticoid secreted by the adrenal cortex. Glucocorticoids are involved in multiple biological processes, affecting carbohydrate, protein, lipid and water metabolism. Cortisol secretion is under the control of adrenocorticotropin (ACTH) which in turn is regulated by the secretion of corticotropin-releasing hormone (CRF) (Figure 1A). Secretion of ACTH and cortisol is pulsatile, manifests a diurnal circadian rhythm, and is under negative feedback control. Stress in a variety of forms can override the diurnal rhythm as well as the negative feedback relationship of the system.
Figure 1. The hypothalamic-pituitary-adrenal axis. Secretion of corticotropin-releasing hormone (CRF) normally regulates secretion of ACTH, which in turn controls cortisol production (A). The system is subject to negative feedback control: Reduced levels of cortisol result in diminished feedback regulation (dashed lines) and marked increases in ACTH levels in primary adrenocortical insufficiency. Levels of melanocyte-stimulating hormone (MSH) lipotropin (BLPH) also increase, resulting in hyperpigmentation (B). Hypothalamic-pituitary disorders that diminish ACTH secretion result in secondary adrenocortical insufficiency (C).
Aldosterone is the principal mineralocorticoid hormone secreted by the adrenal cortex. Normally, the renin-angiotensin system is the major factor controlling aldosterone secretion (Figure 2). Renin is released from the juxtaglomerular cells of the kidney in response to a reduction in renal perfusion pressure, a decrease in effective circulating volume or sympathetic stimulation. Renin enzymatically cleaves the hepatic renin substrate (angiotensinogen) to liberate a decapeptide, angiotensin I. Removal of the carboxy terminal dipeptide by an endothelial converting enzyme produces the octapeptide angiotensin II. Angiotensin II stimulates the zona glomerulosa of the adrenal gland directly to increase aldosterone secretion. Aldosterone increases transepithelial transport of sodium by the kidney, and the resultant sodium retention tends to ameliorate the initial stimulus fir renin secretion. Increases in plasma K+ concentration normally increase aldosterone secretion, whereas hypokalaemia suppresses it. Inasmuch as aldosterone promotes K+ secretion by the kidney, this provides a second feedback mechanism regulating aldosterone secretion. When stimulation by the renin-angiotensin system is reduced during periods of recumbency, plasma aldosterone concentration correlates with the pulsatile release of cortisol, implying that ACTH also plays a role in the physiological regulation of aldosterone secretion.
Figure 2. The renin-angiotensin-aldosterone system. Aldosterone secretion is principally regulated by the renin-angiotensin system. Potassium (K+) and ACTH also stimulate aldosterone secretion, whereas sodium and dopamine (not shown) may inhibit it. Negative feedback occurs by virtue of mineralocorticoid-induced kaliuresis and sodium retention, which reduce levels of K+ and angiotensin II (AII), respectively.
Dr. Afsaneh Jeddi