Adrenal Glands

The paired adrenal (suprarenal) glands, one of which lies superior to each kidney in the retroperitoneal space, have a flattened pyramidal shape. In an adult, each adrenal gland is 3–5 cm in height, 2–3 cm in width, and a little less than 1 cm thick, with a mass of 3.5–5 g, only half its size at birth. During embryonic development, the adrenal glands differentiate into two structurally and functionally distinct regions: a large, peripherally located adrenal cortex, comprising 80–90% of the gland, and a small, centrally located adrenal medulla. A connective tissue capsule covers the gland. The adrenal glands, like the thyroid gland, are highly vascularized.

The adrenal cortex produces steroid hormones that are essential for life. Complete loss of adrenocortical hormones leads to death due to dehydration and electrolyte imbalances in a few days to a week, unless hormone replacement therapy begins promptly. The adrenal medulla produces three catecholamine hormones—norepinephrine, epinephrine, and a small amount of dopamine.

The adrenal cortex is subdivided into three zones, each of which secretes different hormones. The outer zone, just deep to the connective tissue capsule, is the zona glomerulosa. Its cells, which are closely packed and arranged in spherical clusters and arched columns, secrete hormones called mineralocorticoids because they affect mineral homeostasis. The middle zone, or zona fasciculata, is the widest of the three zones and consists of cells arranged in long, straight columns. The cells of the zona fasciculata secrete mainly glucocorticoids, so named because they affect glucose homeostasis. The cells of the inner zone, the zona reticularis, are arranged in branching cords. They synthesize small amounts of weak androgens, steroid hormones that have masculinizing effects.

Aldosterone is the major mineralocorticoid. It regulates homeostasis of two mineral ions, namely sodium ions (Na+) and potassium ions (K+), and helps adust blood pressure and blood volume. Aldosterone also promotes excretion of H in the urine; this removal of acids from the body can help prevent acidosis (blood pH below 7.35).

The renin–angiotensin–aldosterone or RAA pathway controls secretion of aldosterone:

1. Stimulii that initate the renin-angiostensin-aldosterone pathway include dehydration, Na+ deficiency, or hemorrhage.

2. These conditions cause a decrease in blood volume.

3. Decreased blood volume leads to decreased blood pressure.

4. Lowered blood pressure stimulates certain cells of the kidneys, called juxtaglomerular cells, to secrete the enzyme renin.

5. The level of renin in the blood increases.

6. Renin converts angiotensinogen, a plasma protein produced by the liver, into angiotensin I.

7. Blood containing increased levels of angiotensin I circulates in the body.

8. As blood flows through capillaries, particularly those of the lungs, the enzyme angiotensin-converting enzyme (ACE) converts angiotensin I into the hormone angiotensin II.

9. Blood level of angiotensin II increases.

10. Angiotensin II stimulates the adrenal cortex to secrete aldosterone.

11. Blood containing increased levels of aldosterone circulates to the kidneys.

12. In the kidneys, aldosterone increases reabsorption of Na+ and water so that less is lost in the urine. Aldosterone also stimulates the kidneys to increase secretion of K+ and H+ into the urine

13. With increased water reabsorption by the kidneys, blood volume increases.

14. As blood volume increases, blood pressure increases to normal.

15. Angiotensin II also stimulates contraction of smooth muscle in the walls of arterioles. The resulting vasoconstriction of the arterioles increases blood pressure and thus helps raise blood pressure to normal.

16. Besides angiotensin II, a second stimulator of aldosterone secretion is an increase in the K+ concentration of blood (or interstitial fluid). A decrease in the blood K+ level has the opposite effect.

The glucocorticoids, which regulate metabolism and resistance to stress, include cortisol (hydrocortisone), corticosterone, and cortisone. Of these three hormones secreted by the zona fasciculata, cortisol is the most abundant, accounting for about 95% of glucocorticoid activity.

Control of glucocorticoid secretion occurs via a typical negative feedback system. Low blood levels of glucocorticoids, mainly cortisol, stimulate neurosecretory cells in the hypothalamus to secrete corticotropin-releasing hormone (CRH). CRH (together with a low level of cortisol) promotes the release of ACTH from the anterior pituitary. ACTH flows in the blood to the adrenal cortex, where it stimulates glucocorticoid secretion. (To a much smaller extent, ACTH also stimulates secretion of aldosterone.)

Glucocorticoids have the following effects:

1. Protein breakdown. Glucocorticoids increase the rate of protein breakdown, mainly in muscle fibers, and thus increase the liberation of amino acids into the bloodstream. The amino acids may be used by body cells for synthesis of new proteins or for ATP production.

2. Glucose formation. Upon stimulation by glucocorticoids, liver cells may convert certain amino acids or lactic acid to glucose, which neurons and other cells can use for ATP production. Such conversion of a substance other than glycogen or another monosaccharide into glucose is called gluconeogenesis.

3. Lipolysis. Glucocorticoids stimulate lipolysis, the breakdown of triglycerides and release of fatty acids from adipose tissue into the blood.

4. Resistance to stress. Glucocorticoids work in many ways to provide resistance to stress. The additional glucose supplied by the liver cells provides tissues with a ready source of ATP to combat a range of stresses, including exercise, fasting, fright, temperature extremes, high altitude, bleeding, infection, surgery, trauma, and disease. Because glucocorticoids make blood vessels more sensitive to other hormones that cause vasoconstriction, they raise blood pressure. This effect would be an advantage in cases of severe blood loss, which causes blood pressure to drop.

5. Anti-inflammatory effects. Glucocorticoids inhibit white blood cells that participate in inflammatory responses. Unfortunately, glucocorticoids also retard tissue repair, and as a result, they slow wound healing. Although high doses can cause severe mental disturbances, glucocorticoids are very useful in the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

6. Depression of immune responses. High doses of glucocorticoids depress immune responses. For this reason, glucocorticoids are prescribed for organ transplant recipients to retard tissue rejection by the immune system.

In both males and females, the adrenal cortex secretes small amounts of weak androgens. The major androgen secreted by the adrenal gland is dehydroepiandrosterone (DHEA). After puberty in males, the androgen testosterone is also released in much greater quantity by the testes. Thus, the amount of androgens secreted by the adrenal gland in males is usually so low that their effects are insignificant. In females, however, adrenal androgens play important roles. They promote libido (sex drive) and are converted into estrogens (feminizing sex steroids) by other body tissues. After menopause, when ovarian secretion of estrogens ceases, all female estrogens come from conversion of adrenal androgens. Adrenal androgens also stimulate growth of axillary and pubic hair in boys and girls and contribute to the prepubertal growth spurt. Although control of adrenal androgen secretion is not fully understood, the main hormone that stimulates its secretion is ACTH.

The inner region of the adrenal gland, the adrenal medulla, is a modified sympathetic ganglion of the autonomic nervous system (ANS). It develops from the same embryonic tissue as all other sympathetic ganglia, but its cells, which lack axons, form clusters around large blood vessels. Rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones. The hormone-producing cells, called chromaffin cells, are innervated by sympathetic preganglionic neurons of the ANS. Because the ANS exerts direct control over the chromaffin cells, hormone release can occur very quickly.

The two major hormones synthesized by the adrenal medulla are epinephrine and norepinephrine (NE), also called adrenaline and noradrenaline, respectively. The chromaffin cells of the adrenal medulla secrete an unequal amount of these hormones—about 80% epinephrine and 20% norepinephrine. Unlike the hormones of the adrenal cortex, the hormones of the adrenal medulla are not essential for life since they only intensify sympathetic responses in other parts of the body.

In stressful situations and during exercise, impulses from the hypothalamus stimulate sympathetic preganglionic neurons, which in turn stimulate the chromaffin cells to secrete epinephrine and norepinephrine. These two hormones greatly augment the fight-or-flight response. By increasing heart rate and force of contraction, epinephrine and norepinephrine increase the output of the heart, which increases blood pressure. They also increase blood flow to the heart, liver, skeletal muscles, and adipose tissue; dilate airways to the lungs; and increase blood levels of glucose and fatty acids.