The adrenal glands are glandular and neuroendocrine tissue adhering to the top of the kidneys by a fibrous capsule. The adrenal glands have a rich blood supply and have one of the highest rates of blood flow in the body.
Adrenal Glands
They are supplied by several arteries branching off the aorta, including the suprarenal and renal arteries. Blood first flows through the adrenal cortex and then drains into the adrenal medulla. Adrenal hormones are released into the circulation via the left and right suprarenal veins.
The adrenal gland consists of an outer cortex of glandular tissue and an inner medulla of nervous tissue. The cortex itself is divided into three zones: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Each region secretes its own set of hormones.
The adrenal cortex, as a component of the hypothalamic-pituitary-adrenal (HPA) axis, secretes steroid hormones important for the regulation of the long-term stress response, blood pressure and blood volume, nutrient uptake and storage, fluid and electrolyte balance, and inflammation. The HPA axis involves the hypothalamus stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary. ACTH then stimulates the adrenal cortex to produce the hormone from the cortex (corticosteroids). This pathway will be discussed in more detail below.
The adrenal medulla is neuroendocrine tissue composed of postganglionic sympathetic neurons. It is really an extension of the autonomic nervous system. This neuroendocrine pathway, controlled by the hypothalamus, involves stimulation of the medulla by impulses from preganglionic sympathetic neurons originating in the thoracic spinal cord. Stimulation causes the medulla to secrete the amine hormones epinephrine and norepinephrine.
One of the major functions of the adrenal gland is to respond to stress. Stress can be either physical, psychological or both. Physical stresses may include injury, exposure to severe temperatures or malnutrition. Psychological stresses include the perception of a physical threat, a fight with a loved one, or just a bad day at school.
The body responds in different ways to short-term stress and long-term stress following a pattern known as the general adaptation syndrome (GAS). Stage one of GAS is called the alarm reaction. This is short-term stress, the fight-or-flight response, mediated by the hormones epinephrine and norepinephrine from the adrenal medulla. Their function is to prepare the body for extreme physical exertion. Once this stress is relieved, the body quickly returns to normal. The section on the adrenal medulla covers this response in more detail.
If the stress is not soon relieved, the body adapts to the stress in the second stage called the stage of resistance. If a person is starving for example, the body may send signals to the gastrointestinal tract to maximize the absorption of nutrients from food.
If the stress continues for a longer term however, the body responds with symptoms quite different than the fight-or-flight response. During the stage of exhaustion, individuals may begin to suffer depression, the suppression of their immune response, severe fatigue, or even a fatal heart attack. These symptoms are mediated by the hormones of the adrenal cortex, especially cortisol, released as a result of signals from the HPA axis.
Adrenal hormones also have several non–stress-related functions, including the increase of blood sodium and glucose levels, which will be described in detail below.
Adrenal Cortex
The adrenal cortex consists of multiple layers of lipid-storing cells that occur in three structurally distinct regions. Each of these regions produces different hormones.
Hormones of the Zona Glomerulosa
The most superficial region of the adrenal cortex is the zona glomerulosa, which produces a group of hormones collectively referred to as mineralocorticoids because of their effect on body minerals, especially sodium and potassium. These hormones are essential for fluid and electrolyte balance.
Aldosterone is the major mineralocorticoid. It is important in the regulation of the concentration of sodium and potassium ions in urine, sweat, and saliva. For example, it is released in response to elevated blood K+, low blood pressure or low blood volume. In response, aldosterone increases the excretion of K+ and the retention of Na+, which in turn increases blood volume and blood pressure. Release of aldosterone is primarily controlled indirectly by the kidney in response to decreased blood pressure or directly by increased blood potassium. However, during a stress response its secretion is prompted when CRH from the hypothalamus triggers ACTH release from the anterior pituitary.
Aldosterone is also a key component of the renin-angiotensin-aldosterone system (RAAS) in which specialized cells of the kidneys secrete the enzyme renin in response to low blood volume or low blood pressure. Renin then catalyzes the conversion of the blood protein angiotensinogen, produced by the liver, to the hormone angiotensin I. Angiotensin I is converted in the lungs to angiotensin II by angiotensin-converting enzyme (ACE). In addition to stimulating aldosterone release from the adrenal cortex thus increasing blood volume and pressure, angiotensin II is a potent vasoconstrictor.
For individuals with hypertension, or high blood pressure, drugs are available that block the production of angiotensin II. These drugs, known as ACE inhibitors, block the ACE enzyme from converting angiotensin I to angiotensin II, thus mitigating the latter’s ability to increase blood pressure.
Hormones of the Zona Fasciculata
The intermediate region of the adrenal cortex is the zona fasciculata, named as such because the cells form small fascicles (bundles) separated by tiny blood vessels. The cells of the zona fasciculata produce hormones called glucocorticoids because of their role in glucose metabolism. The most important of these is cortisol, some of which the liver converts to cortisone. A glucocorticoid produced in much smaller amounts is corticosterone. In response to long-term stressors, the hypothalamus secretes CRH, which in turn triggers the release of ACTH by the anterior pituitary. ACTH triggers the release of the glucocorticoids. Their overall effect is to inhibit tissue building while stimulating the breakdown of stored nutrients to maintain adequate fuel supplies. In conditions of long-term stress, for example, cortisol promotes the catabolism of glycogen to glucose, the catabolism of stored triglycerides into fatty acids and glycerol, and the catabolism of muscle proteins into amino acids. These raw materials can then be used to synthesize additional glucose and ketones for use as body fuels. The hippocampus, which is part of the temporal lobe of the cerebral cortices and important in memory formation, is highly sensitive to stress levels because of its many glucocorticoid receptors.
You are probably familiar with prescription and over-the-counter medications containing glucocorticoids, such as cortisone injections into inflamed joints, prednisone tablets and steroid-based inhalers used to manage severe asthma, and hydrocortisone creams applied to relieve itchy skin rashes. These drugs reflect another role of cortisol—the suppression of the immune system, which inhibits the inflammatory response.
Hormones of the Zona Reticularis
The deepest region of the adrenal cortex is the zona reticularis, which produces small amounts of a class of steroid sex hormones called androgens. During puberty and most of adulthood, androgens are produced in the gonads. The androgens produced in the zona reticularis supplement the gonadal androgens. They are produced in response to ACTH from the anterior pituitary and are converted in the tissues to testosterone or estrogens. In adult women, they may contribute to the sex drive, but their function in adult men is not well understood. In post-menopausal women, as the functions of the ovaries decline, the main source of estrogens becomes the androgens produced by the zona reticularis.
Adrenal Medulla
As noted earlier, the adrenal cortex releases glucocorticoids in response to long-term stress such as severe illness. In contrast, the adrenal medulla releases its hormones in response to acute, short-term stress mediated by the sympathetic nervous system (SNS).
The medullary tissue is composed of modified postganglionic neurons called chromaffin cells, which are large and irregularly shaped, and produce the neurotransmitters epinephrine (also called adrenaline) and norepinephrine (or noradrenaline). Epinephrine is produced in greater quantities—approximately a 4 to 1 ratio with norepinephrine—and is the more powerful hormone. Because the chromaffin cells release epinephrine and norepinephrine into the systemic circulation, where they travel widely and exert effects on distant cells, they are considered hormones. Derived from the amino acid tyrosine, they are chemically classified as catecholamines.
The secretion of medullary epinephrine and norepinephrine is controlled by a neural pathway that originates from the hypothalamus in response to danger or stress. Both epinephrine and norepinephrine signal the liver and skeletal muscle cells to convert glycogen into glucose, resulting in increased blood glucose levels. These hormones increase heart rate and blood pressure to prepare the body to fight the perceived threat or flee from it. In addition, the pathway dilates the airways, raising blood oxygen levels. It also prompts vasodilation, further increasing the oxygenation of organs essential to fight or flight such as the lungs, brain, heart, and skeletal muscle. At the same time, it triggers vasoconstriction to blood vessels supplying organs less essential to fight or flight such as the gastrointestinal tract, kidneys, and skin. Other effects include a dry mouth, loss of appetite, pupil dilation, and a loss of peripheral vision. The major hormones of the adrenal glands are summarized in.
| Hormones of the Adrenal Glands | |||
|---|---|---|---|
| Adrenal gland | Associated hormones | Chemical class | Effect |
| Adrenal cortex | Aldosterone | Steroid | Increases blood Na+ levels |
| Adrenal cortex | Cortisol, corticosterone, cortisone | Steroid | Increase blood glucose levels |
| Adrenal cortex | Androgens | Steroid | Female Libido and Postmenopausal Estrogen |
| Adrenal medulla | Epinephrine, norepinephrine | Amine | Stimulate fight-or-flight response |
Disorders Involving the Adrenal Glands
Several disorders are caused by the dysregulation of the hormones produced by the adrenal glands. For example, Cushing’s disease is a disorder characterized by high blood glucose levels and the accumulation of lipid deposits on the face and neck. It is caused by hypersecretion of cortisol. The most common source of Cushing’s disease is a pituitary tumor that secretes ACTH in abnormally high amounts. Other common signs of Cushing’s disease include the development of a moon-shaped face, a buffalo hump on the back of the neck, rapid weight gain, and hair loss. Chronically elevated glucose levels are also associated with an elevated risk of developing type 2 diabetes. In addition to hyperglycemia, chronically elevated glucocorticoids compromise immunity, resistance to infection, and memory, and can result in rapid weight gain and hair loss. Long term glucocorticoid use for inflammatory conditions such as rheumatoid arthritis or to prevent transplant rejection can cause symptoms similar to those in Cushing’s disease.
In contrast, the hyposecretion of corticosteroids can result in Addison’s disease, a rare disorder that causes low blood glucose levels and low blood sodium levels. The signs and symptoms of Addison’s disease are vague and are typical of other disorders as well, making diagnosis difficult. They may include general weakness, abdominal pain, weight loss, nausea, vomiting, sweating, and cravings for salty food. Treatment involves injections of glucocorticoids.
Bhaskar Summary
The adrenal glands, located superior to each kidney, consist of two regions: the adrenal cortex and adrenal medulla. The adrenal cortex—the outer layer of the gland—produces mineralocorticoids, glucocorticoids, and androgens. The adrenal medulla at the core of the gland produces epinephrine and norepinephrine.
The adrenal glands mediate a short-term stress response and a long-term stress response. A perceived threat results in the secretion of epinephrine and norepinephrine from the adrenal medulla, which mediate the fight-or-flight response. The long-term stress response is mediated by the secretion of CRH from the hypothalamus, which triggers ACTH, which in turn stimulates the secretion of corticosteroids from the adrenal cortex. The mineralocorticoids, chiefly aldosterone, cause sodium and fluid retention, which increases blood volume and blood pressure.
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