Adrenal Gland Anatomy and Function

Adrenal Gland Basics

• Small, triangular-shaped glands found near the kidneys.
• Retroperitoneal, similar to kidneys, with only the ventral surface contacting the parietal peritoneum.
• Named "adrenal" due to their proximity to the kidneys.
• Outer cortex produces steroid hormones like cortisol and aldosterone.
• Inner medulla synthesizes catecholamines, including adrenaline (epinephrine) and noradrenaline (norepinephrine).

Development

• The cortex originates from mesodermal tissue and releases steroid hormones, regulated by the anterior pituitary.
• The medulla is derived from neuronal tissue, forming a functional part of the sympathetic nervous system that releases adrenaline (epinephrine) and noradrenaline (norepinephrine).

Adrenal Cortex Zones

• The adrenal cortex contains three distinct zones.
• The zona glomerulosa produces mineralocorticoids.
• The zona fasciculata synthesizes glucocorticoids.
• The zona reticularis creates androgens.

Adrenocortical Hormones

• Adrenocortical hormones are steroid hormones derived from cholesterol.
• The production of these hormones involves multiple intermediate steps.
• These steps are influenced by various enzymes.
• Each cortical region synthesizes a specific end-product hormone.

Hormone Synthesis Regulation

• All hormones have the basic steroid carbon skeleton with A, B, C, and D carbon rings.
• Each hormone is produced through a modification of its basic structure, beginning with cholesterol.
• The initial step involves removing the cholesterol side chain (C22-C27), forming pregnenolone.
• This occurs in the mitochondria of adrenocortical cells and is regulated by adrenocorticotropic hormone (ACTH) in the inner zones and Angiotensin II in the outermost zone.
• The hormones are lipid-soluble.

ACTH's Role

• ACTH is part of the hypothalamic-pituitary-adrenal axis, involving the hypothalamus, pituitary, and adrenal glands.
• Stress initiates its release.
• The hypothalamus releases corticotropic-releasing hormone (CRH).
• CRH travels to the anterior pituitary.
• This stimulates the release of ACTH.
• ACTH acts on the zona fasciculata and zona reticularis cells via a G-protein coupled receptor.
• ACTH increases cholesterol uptake, the transcription of the first-step enzyme (P450scc), and the conversion of cholesterol into glucocorticoids and androgens.
• Glucocorticoids and ACTH create negative feedback to the pituitary and hypothalamus.

Renin-Angiotensin System

• Renin is released by juxtaglomerular cells, which converts angiotensinogen to angiotensin I.
• Angiotensin-converting enzyme (ACE), found in pulmonary capillaries, converts angiotensin I to angiotensin II.
• Angiotensin II stimulates aldosterone production in the zona glomerulosa of the adrenal cortex.
• This process is triggered by sustained blood pressure drops or high potassium levels.

Mineralocorticoids (Aldosterone)

• Mineralocorticoids maintain homeostasis of inorganic ions (Na+, K+, Cl-).
• Aldosterone, produced in the zona glomerulosa, is the most active hormone.
• ACTH is required for aldosterone secretion but has little impact on the rate of secretion.
• The renin-angiotensin system and extracellular potassium levels primarily regulate secretion.

Aldosterone Production

• Aldosterone is produced in the zona glomerulosa of the adrenal gland.
• It is secreted in response to the activation of the renin-angiotensin-aldosterone system.

Aldosterone Action on Renal Tubule Cells

• Systemic hypotension or high K+ intake stimulates
• Aldosterone to cross the basolateral membrane of renal tubule cells.
• Aldosterone then binds to a mineralocorticoid nuclear receptor and activates transcription and synthesis of new Na+ channels, K+ channels, and Na+/K+ pumps.
• Consequently, Na+ reabsorption increases, and K+ secretion increases.

Glucocorticoids (Cortisol)

• The most important glucocorticoid in domestic mammals is cortisol.
• Corticosterone is found in birds and rodents.
• Cortisol binds to, and is transported by, cortisol-binding globulin (CBG) for a longer half-life.
• Release follows circadian rhythms but is less pronounced in domestic species than in humans.
• Stress is the main stimulus for release.

Cortisol Action in the Body

• All nucleated cells contain cortisol receptors.
• Cortisol molecules are lipid-soluble and diffuse across the cell membrane to bind with cortisol receptors.
• The cortisol-receptor complex binds to DNA, influencing gene transcription.
• Glucocorticoids are essential and exert multiple effects.

Cortisol as a Stress Hormone

• Cortisol is important during stress, increasing plasma levels affecting digestion, blood pressure, and energy resources.
• Cortisol allows catecholamines to induce vasoconstriction.
• It increases plasma glucose levels, stimulates gluconeogenesis, and inhibits glucose uptake (except in the brain).
• Cortisol stimulates fat and protein degradation for energy, increasing fatty acid availability and using glycerol and amino acids as substrates for gluconeogenesis.
• It inhibits DNA synthesis.
• High levels reduce inflammation and allergic responses (immunosuppression).

Glucocorticoids as Anti-Inflammatory Drugs

• Glucocorticoid derivatives, like dexamethasone, treat arthritis and asthma.
• Chronically high levels cause skin weakening, muscle wasting, reduced bone strength, immunosuppression, and damage to hippocampal nerve cells.
• Long-term use requires careful monitoring, especially in children, to avoid affecting normal growth.

Androgens

• The zona reticularis secretes the androgen dehydroepiandrosterone (DHEA).
• DHEA and androstenedione act as a source of androgens in females, supporting hair growth and libido.
• They are less important in males due to the presence of testosterone.

Adrenal Medulla

• The adrenal medulla is derived from the sympathetic nervous system.
• It synthesizes and secretes catecholamines.
• Adrenaline (epinephrine) accounts for 80% of the production.
• Noradrenaline (norepinephrine) is 20% of the production.
• Catecholamine-producing cells are chromaffin cells derived from Tyrosine.
• Cortisol stimulates production of a rate-limiting enzyme in the process.

Adrenal Medullary Hormones

• Adrenaline (Epinephrine) is released in response to short-term stress, increasing heart rate and contraction force, blood flow to muscles and the brain, smooth muscle relaxation and conversion of glycogen to glucose in the liver.
• Noradrenaline (Norepinephrine) causes vasoconstriction to maintain blood pressure.
• Its production is elevated in response to acute stress.

Adrenocortical Secretion Abnormalities

• Hyperadrenocorticism results in Cushing's Disease, involving an overproduction of glucocorticoids.
• Hypoadrenocorticism results in Addison's Disease, stemming from a deficiency of glucocorticoids and mineralocorticoids.

Common Adrenal Gland Issues

• Excessive glucocorticoid production can cause Cushing's Disease.
• It can be caused by local adrenal tumors, pituitary tumors (↑ACTH), or prolonged steroid treatment.
• Insufficient mineralocorticoid or glucocorticoid production causes Addison's Disease.
• It is caused by autoimmune issues, may be congenital, or happen after stopping steroid treatment (tapered stop).
• Pheochromocytoma also can occur.
• Results from excessive catecholamine production, typically from benign medullary tumors.