96 The Adrenal (Suprarenal) Glands

Overview of the Adrenal Glands

In mammals, the adrenal glands (also known as the suprarenal glands) are endocrine glands that sit atop the kidneys.

In mammals, the adrenal glands (also known as the suprarenal glands) are endocrine glands that sit atop the kidneys. They are chiefly responsible for releasing three classes of hormones:

1. Mineralocorticoids (aldosterone)
2. Glucocorticoids (cortisol)
3. Androgens (DHEA)

Along with catecholamines (adrenaline), these hormones control a variety of functions including kidney function, metabolism, fight-or-flight response, and sex hormone levels.

In humans, the adrenal glands are found at the level of the 12th thoracic vertebra sitting above and slightly medial to the kidneys, lying within the renal fascia, and separated from the kidneys by a thin layer of connective tissue. In humans, the right adrenal gland is triangular shaped, while the left adrenal gland is semilunar shaped.

Each adrenal gland has two distinct structures, the outer adrenal cortex and the inner medulla—both produce hormones. The cortex mainly produces mineralcorticoids, glucocorticoids, and androgens, while the medulla chiefly produces adrenaline and nor-adrenaline.

Adrenal Cortex

The adrenal cortex is devoted to the synthesis of corticosteroid and androgen hormones.

Zones of the Adrenal Cortex

The cortex is regulated by neuroendocrine hormones secreted by the pituitary gland, which are under the control of the hypothalamus, as well as by the renin- angiotensin system. The adrenal cortex has three zones or layers:

1. Zona glomerulosa (outer)
2. Zona fasciculata
3. Zona reticularis

Zona Glomerulosa

The outermost layer, the zona glomerulosa, is the main site for production of mineralocorticoids, mainly aldosterone, that are largely responsible for the long-term regulation of blood pressure.

Aldosterone exerts its effects on the distal convoluted tubule and collecting duct of the kidney, where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). The major stimulus to produce aldosterone is angiotensin II, as ACTH from the pituitary only produces a transient effect. Angiotensin is stimulated by the juxtaglomerular cells when renal blood pressure drops below 90 mmHg.

Zona Fasciculata

Zona fasciculata is the layer situated between the glomerulosa and reticularis. This layer is responsible for producing glucocorticoids, such as 11-deoxycorticosterone, corticosterone, and cortisol in humans. Cortisol enhances the activity of other hormones including glucagon and catecholamines.

Zona Reticularis

Zona reticularis is the innermost cortical layer, and it produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.

Hormones of the Adrenal Cortex

The different zones of the adrenal cortex produce different hormones.

Mineralocorticoids

These are produced in the zona glomerulosa. The primary mineralocorticoid is aldosterone. Its secretion is regulated by the oligopeptide angiotensin II. Aldosterone is secreted in response to high extracellular potassium levels, low extracellular sodium levels, and low fluid levels and blood volume. Aldosterone secretion affects metabolism in different ways:

• It increases urinary excretion of potassium ions
• It increases interstitial levels of sodium ions
• It increases water retention and blood volume.

Glucocorticoids

These are produced in the zona fasciculata. The primary glucocorticoid released by the adrenal gland in humans is cortisol. Its secretion is regulated by the hormone ACTH from the anterior pituitary gland. Upon binding to its target, cortisol enhances metabolism in several ways:

• It stimulates the release of amino acids from the body
• It stimulates lipolysis, the breakdown of fat
• It stimulates gluconeogenesis, the production of glucose from newly-released amino acids and lipids
• It increases blood glucose levels in response to stress, by inhibiting glucose uptake into muscle and fat cells
• It strengthens cardiac muscle contractions
• It increases water retention
• It has anti-inflammatory and anti-allergic effects.

Androgens

The zona reticularis produces androgens, the most important of which is
DHEA. In general, these hormones do not have an overall effect in the male body, and are converted to more potent androgens such astestosterone and DHT or to estrogens (female sex hormones) in the gonads, acting in this way as a metabolic intermediate.

Adrenal Medulla

The adrenal cortex is devoted to the synthesis of corticosteroid and androgen hormones.

The adrenal medulla is the core of the adrenal glands, and is surrounded by the adrenal cortex. The adrenal medulla is responsible for the production of catecholamines, derived from the amino acid tyrosine.

These water-soluble hormones are the major hormones underlying the fight-or-flight response. The adrenal medulla secretes approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine). To carry out this response, the adrenal medulla receives input from the sympathetic nervous system through nerve fibers originating in the thoracic spinal cord from T5–T11.

Chromaffin cells are the neuroendocrine cells found in the medulla; they are modified post-synaptic sympathetic neurons that receive sympathetic input.

When stimulated, chromaffin cells secrete adrenaline and noradrenaline along with enkephalin and enkephalin-containing peptides into the bloodstream. The secreted adrenaline and noradrenaline play an important role in the fight-or-flight response.

The enkephalins and enkephalin-containing peptides are related to, but also distinct from, the endogenous peptides named endorphins (secreted from the pituitary). All of these peptides bind to opioid receptors and produce analgesic (and other) responses.

Some notable effects of adrenaline and noradrenaline include:

• Increased heart rate and blood pressure.
• Blood vessel constriction in the skin and gastrointestinal tract.
• Smooth muscle dilation.
• Dilating bronchioles and capillaries.
• Increased metabolism.

All of these effects are characteristic of the fight-or-flight response. Receptors for catecholamines are widely distributed throughout the body to allow for a systemic response following secretion.