Adrenal Glands and Hormones Overview

The Adrenal Gland and Adrenal Hormones

• Aldosterone, epinephrine, and norepinephrine are hormones.
• Aldosterone is a mineralocorticoid.
• Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex.
• Aldosterone regulates extracellular volume by its effect on sodium reabsorption by the kidney and impacts water balance.
• The renin-angiotensin system is a major regulator of aldosterone secretion.
• The five adrenoceptor subtypes respond differently to adrenaline and noradrenaline.
• Adrenaline and noradrenaline are involved in the 'fight or flight' response
• Cortisol and aldosterone are produced from cholesterol.
• Aldosterone is not stored, secretion rate is governed by synthesis rate in the glomerulosa cells.
• ACTH, extracellular potassium and sodium and Angiotensin II stimulate aldosterone production.
• Enzymes like SCC enzyme and aldosterone synthase, are key in aldosterone production process.
• 37% of circulating aldosterone is free in plasma.
• Aldosterone's primary action is stimulating the kidney to reabsorb sodium and water and to increase potassium secretion.
• Aldosterone impacts distal tubule and collecting duct Na+ reabsorption
• Imbalances can result in significant electrolyte abnormalities.
• Aldosterone affects target renal tubular cells by influencing sodium-transport proteins (e.g. Na+/K+ pump).

Synthesis of Aldosterone

• Aldosterone synthesis occurs exclusively in glomerulosa cells of the adrenal cortex.
• The rate of aldosterone secretion is controlled by synthesis rate.
• ACTH, extracellular potassium and sodium levels, and angiotensin II are stimulatory factors.
• Enzymes SCC enzyme and aldosterone synthase are important in rate-limiting synthesis steps
• ~37% of circulating aldosterone is free in the plasma
• The remaining portion binds to CBG (21%) and albumin (42%).

Mechanism of Action of Aldosterone

• Aldosterone acts by modulating gene transcription after binding to Mineralocorticoid receptors (MR).
• It regulates only a small portion of renal sodium reabsorption that happens in the distal tubule and collecting duct.
• Loss of aldosterone's effect can lead to significant electrolyte abnormalities.
• Excess aldosterone leads to hypokalemia and hypertension.

Mechanism of Action of Aldosterone (detailed)

• Aldosterone increases transcription of the Na-K pump and enhances expression of sodium channels and Na/K/Cl transporter.
• These actions increase sodium reabsorption and potassium secretion.
• ROMK = renal outer medullary potassium channel
• ENaC = epithelial sodium channel
• Key proteins involved in sodium transport are enhanced by aldosterone.

Zona Glomerulosa Aldosterone: Regulation

• Nat and water levels are regulated through the renin-angiotensin system (RAS).
• Angiotensin II binds to a receptor, triggering a cascade that increases intracellular calcium concentration.
• Calcium increases, stimulating the production of P450scc (desmolase, CYP11A1), and delivery of cholesterol/aldosterone synthase.
• High extracellular potassium depolarizes glomerulosa cells.
• Voltage gated calcium channels open and then stimulate production of P450scc and cholesterol/aldosterone synthase.
• ACTH also stimulates aldosterone synthesis
• Binding to MC2R stimulates calcium influx.

Regulation of Aldosterone Synthesis (detailed)

• The hypothalamus, pituitary gland (ACTH), and renin-angiotensin system control aldosterone synthesis.
• Increased blood volume or pressure, low blood sodium, or high blood potassium stimulate aldosterone synthesis.
• Decreased blood pressure , Na+, or increased K+ trigger different pathways
• Other pathways such as direct stimulation, or inhibitory effects also play a part.

Feedback Regulation of Aldosterone Synthesis

• Blood levels of potassium ([K+]) and sodium ([Na+]) are monitored to regulate aldosterone.
• High [K+] stimulates aldosterone release, whereas high [Na+] inhibits it.
• Changes in blood volume and blood pressure affect aldosterone synthesis.

The Adrenal Medulla: Catecholamines

• The adrenal medulla synthesizes and secretes epinephrine and norepinephrine in response to stress, exercise, and hypoglycemia.
• Chromaffin cells are responsible for catecholamine production and secretion.
• Norepinephrine and epinephrine are synthesized through a series of enzymes (tyrosine hydroxylase, DOPA decarboxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl transferase.
• Catecholamines are stored in chromaffin granules.
• Epinephrine accounts for the majority, 70-80%

Development of the Adrenal Gland (AG)

• Adrenal cortex develops from mesoderm.
• Chromaffin cells (neural crest origin) migrate into cortical cells, forming the adrenal medulla.
• Cortisol from the adrenal cortex inhibits the differentiation of chromaffin cells into sympathetic neurons
• Cortisol increases expression of PNMT, leading to conversion of norepinephrine to epinephrine.

The Adrenal medulla

• The adrenal medulla acts as a sympathetic ganglion without postganglionic neurons.
• Catecholamines are secreted directly into the bloodstream.
• The primary signaling is Acetylcholine (ACh),
• ACh increases tyrosine hydroxylase and dopamine β-hydroxylase activity, leading to catecholamine production.

Degradation of Catecholamines

• Catecholamines are degraded quickly (~10 seconds).
• Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the key enzymes.

Mechanism of Action of Catecholamines

• Catecholamines (epinephrine and norepinephrine) bind to adrenergic G protein-coupled receptors (GPCRs).
• Different receptors (e.g., a1, a2, β1, β2, β3) mediate different responses.
• Epinephrine has higher potency on certain receptors (e.g. β2), while norepinephrine has higher potency on others.

Physiologic Actions of Catecholamines

• Catecholamines are involved in the fight-or-flight response.
• Increased blood flow to muscles, increased glucose availability, and decreased energy demand in visceral smooth muscle are some of the key physiological outcomes of norepinephrine and epinephrine.

Pheochromocytoma

• A tumor of the adrenal medulla or other chromaffin tissue.
• Excessive catecholamine production leading to symptoms like hypertension, headaches, sweating, and anxiety.
• Diagnosis involves laboratory detection of urinary catecholamines and treatment may involve surgery.

This quiz covers essential information about adrenal hormones, focusing on aldosterone, epinephrine, and norepinephrine. Test your understanding of their synthesis, regulation, and roles in the body, including the fight or flight response and water balance. Delve into the mechanisms controlling aldosterone production and its physiological impact.