Adrenal Glands: Structure and Function

Overview of the Adrenal Glands

The adrenal glands (also known as suprarenal glands) are pyramid-shaped endocrine organs located atop each kidney. Each adrenal gland is composed of two distinct regions, each with unique structural and functional characteristics:

• Adrenal cortex: The outer region, consisting of three layers of glandular tissue, responsible for synthesizing and secreting various steroid hormones.

• Adrenal medulla: The inner region, made of nervous tissue, is part of the sympathetic nervous system and secretes two amine hormones.

Adrenal hormones play a crucial role in helping the body cope with stressful situations.

Adrenal Cortex

Zones and Hormone Production

The adrenal cortex produces over 24 different steroid hormones, collectively called corticosteroids. These hormones are synthesized as needed and cannot be stored within cells. The cortex is divided into three zones, each producing a distinct class of corticosteroids:

• Zona glomerulosa: Produces mineralocorticoids

• Zona fasciculata: Produces glucocorticoids

• Zona reticularis: Produces gonadocorticoids

Mineralocorticoids

Mineralocorticoids regulate blood electrolyte (mineral salt) concentrations, primarily sodium (Na+) and potassium (K+). Their actions are essential for maintaining fluid balance, blood pressure, and proper cellular function.

• Importance of Na+ regulation: Sodium regulation is coupled to the balance of other ions (K+, H+, HCO3-, Cl-) and water. Water follows sodium, so Na+ levels directly affect blood volume and pressure.

• Importance of K+ regulation: Potassium sets the resting membrane potential of cells, determining how easily action potentials are generated in neurons and muscle cells.

Aldosterone: The Principal Mineralocorticoid

Aldosterone is the most potent mineralocorticoid. It acts mainly by:

• Stimulating synthesis and activation of Na+-K+ ATPase transport pumps (exchanging Na+ for K+) in kidney tubules.

• Increasing Na+ reabsorption by kidneys, which raises blood volume and pressure (as water follows Na+).

• Increasing K+ secretion (and thus excretion) by kidneys.

Regulation of Aldosterone Secretion

Four mechanisms regulate aldosterone secretion (the first two are most important):

1. Renin-angiotensin-aldosterone system (RAAS): A drop in blood pressure triggers kidneys to secrete renin, which converts angiotensinogen (a plasma protein) into angiotensin I. Angiotensin I is then converted to angiotensin II by an enzyme, which stimulates aldosterone release from the zona glomerulosa.

2. Plasma K+ concentration: Rising K+ levels directly stimulate the zona glomerulosa to release aldosterone; decreasing K+ levels inhibit its release.

3. ACTH (adrenocorticotropic hormone): Has little effect except during intense stress, when high blood levels can trigger small amounts of aldosterone release.

4. Atrial natriuretic peptide (ANP): Secreted by the heart in response to high blood pressure; blocks renin and aldosterone secretion to decrease blood pressure.

Homeostatic Imbalance: Aldosteronism

Aldosteronism is hypersecretion of aldosterone, usually due to adrenal tumors. It results in:

• Hypertension and edema due to excessive Na+ retention

• Excessive loss of K+, leading to neurons and muscle weakness (even paralysis)

Glucocorticoids

Glucocorticoids regulate nutrient (energy) metabolism in most cells and help maintain blood glucose levels. They also help maintain blood pressure by increasing the action of vasoconstrictors. Major glucocorticoids include:

• Cortisol (hydrocortisone): The only glucocorticoid secreted in significant amounts in humans

• Cortisone

• Corticosterone

Regulation of Glucocorticoid Secretion

• CRH (corticotropin-releasing hormone) from the hypothalamus stimulates release of ACTH from the anterior pituitary, which triggers cortisol secretion.

• Rising levels of cortisol inhibit release of CRH and ACTH via negative feedback.

• Cortisol secretion cycles are governed by patterns of eating and activity.

• Stressors (infection, physical, or emotional trauma) interrupt cortisol rhythm; the CNS can override negative feedback, leading to more cortisol secretion.

Actions of Cortisol

• Increases blood levels of amino acids and fatty acids by triggering protein breakdown and signaling adipose tissue to break down stored fat.

• Encourages other cells to use fatty acids for fuel, so glucose is "saved" for the brain.

• Main metabolic role: increases blood glucose by signaling the liver to synthesize glucose from amino acids and fatty acids (gluconeogenesis).

• Enhances vasoconstriction by the sympathetic nervous system during stress or hypotension.

• Excessive glucocorticoids depress cartilage and bone formation, inhibit inflammation, depress the immune system, and disrupt cardiovascular, neural, and gastrointestinal functions.

• Glucocorticoid drugs can control symptoms of inflammatory disorders (e.g., rheumatoid arthritis, allergies) but may cause undesirable effects.

Homeostatic Imbalances

• Cushing's syndrome: Excess glucocorticoids, often due to ACTH-releasing tumors or clinical administration of glucocorticoid drugs. Effects include high blood glucose ("steroid diabetes"), muscle and bone protein loss, salt and water retention (hypertension, edema), easy bruising, poor wound healing, and increased risk of infection. Treatment involves tumor removal or discontinuation of drugs.

• Addison's disease: Hyposecretion of corticosteroids, usually affecting both glucocorticoids and mineralocorticoids. Effects include weight loss, decreased blood glucose and Na+ levels, increased K+ levels, severe dehydration, low blood pressure, and characteristic skin bronzing due to high ACTH levels. Treatment is corticosteroid replacement therapy.

Gonadocorticoids

Gonadocorticoids are weak androgens (male sex hormones) such as androstenedione and dehydroepiandrosterone (DHEA). Most are converted to stronger androgens (testosterone) or estrogens in target tissues. Their production by the adrenal cortex is minor compared to gonadal production after puberty.

• Contribute to secondary sex characteristics

• Thought to contribute to sex drive in women

• Main source of estrogens in postmenopausal women

• ACTH triggers release, but there is little negative feedback inhibition

Homeostatic Imbalance: Adrenogenital Syndrome

Adrenogenital syndrome (masculinization) is caused by hypersecretion of gonadocorticoids. Effects are most noticeable in females and prepubertal males:

• Boys: Early maturation of reproductive organs, appearance of secondary sex characteristics, and increased sex drive

• Females: Development of masculine body hair pattern; clitoris enlargement

Adrenal Medulla

Structure and Hormone Production

The adrenal medulla contains chromaffin cells that synthesize catecholamines: epinephrine (80%) and norepinephrine (20%), derived from the amino acid tyrosine. These hormones are secreted in response to stimulation by preganglionic sympathetic neurons during the fight-or-flight (stress) response.

Actions of Catecholamines

• Increase blood pressure via vasoconstriction and increased heart rate

• Divert blood from nonessential organs to heart and skeletal muscle

• Raise blood glucose levels

Homeostatic Imbalances

• Hyposecretion: Not usually problematic, as adrenal catecholamines reinforce norepinephrine from the sympathetic nervous system.

• Hypersecretion: Often caused by tumors of medullary chromaffin cells (pheochromocytoma), leading to uncontrolled sympathetic activity: increased metabolic rate, rapid heartbeat, palpitations, hypertension, intense nervousness, and sweating.

Stress Response

General Adaptation Syndrome

A stressor is any factor (physiological or psychological) that triggers the stress response, coordinated by the hypothalamus. The response includes several stages:

• Short-term stress: Triggers the fight-or-flight response, mediated by the sympathetic nervous system and adrenal catecholamines.

• Long-term stress: Triggers the slower resistance reaction, mediated by adrenal corticosteroids.

• Exhaustion: Prolonged stress can disrupt homeostasis due to the effects of stress hormones themselves.

Summary Table: Adrenal Cortex Zones and Hormones

Key Equations

• Na+-K+ ATPase pump:

• Gluconeogenesis:

Additional info: Some explanations and terminology have been expanded for clarity and completeness, including the summary table and equations.