Notes on Adrenal Hormones

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Layers of the Adrenal Gland:

• Adrenal cortex is divided into 3 zones: zona glomerulosa (outer), zona fasciculata (middle), and zona reticularis.

Zona Glomerulosa:

• 15% of adrenal gland, secretes mainly mineralocorticoids.

Zona Fasciculata:

• 50% of adrenal gland, secretes glucocorticiods.

Zona Reticularis:

• 7% of adrenal gland, secretes androgens.

Role of Cholesterol:

• Cells in all three layers have high lipid content, mainly cholesterol esters.

• Cholesterol is used for the synthesis of steroid hormones.

• This cholesterol is absorbed from: LDL uptake from blood, and synthesis from acetyl-CoA.

• All adrenocortical hormones represent chemical modifications of the steroid nucleus, a 21 carbon atom-4 ring structure derived from cholesterol.

Control of Hormonal Secretion:

• Secretion by zona fasciculata and zona reticularis is mainly controlled by the hypothalamic-pituitary system.

• Secretion by zona reticularis may be controlled by ACTH through a negative-feedback cycle.

• Low blood levels of glucocorticoids, mainly cortisol, stimulate neurosecretory cells in the hypothalamus to secrete corticotroin-releasing hormone, CRH, which promotes release of ACTH from anterior pituitary.

Role of ACTH and Protein Kinase A:

• ACTH flows in the blood to adrenal cortex, stimulating glucocorticoid secretion.

• ACTH binds to its receptors on the plasma membrane of zona fascitulata and reticularis cells, activating protein kinase A.

• Protein kinase A increases activity of cholesterol ester, hydrolase, increasing conversion of cholesterol esters to free cholesterol, which also leads to the formation of pregnenolone, a rate-limiting step in steroid synthesis.

• Thus, cortisol is produced from cholesterol esters.




• Cortisol decrease -adrenalectomy, metyrapone

• Sleep-wake transition

• Stress


• alpha-adrenergic agonists

• beta-adrenergic antagonists

• Others: serotonin, Ach, interleukins, gastrointestinal peptides


• Cortisol increase

• Encephalins


• Opioids


Plasma Cortisol level increased by:

• Factors increasing ACTH production

• Stress

• Surgery

• Burns

• Infection

• Fever

• Psychosis

• Acute anxiety

• Prolonged and strenuous exercise

• Hypoglycaemia

Cortisol Metabolism:

• Cortisol isn't broken down in tissues where it exerts its functions, but is converted to a less active state called cortisone.

• Some is excreted in urine, unchanged.

• Some is degraded in liver to inactive dihydrocortisol and tetrahydrocortisol, which are conjugated with glucuronic acid.

• Thus, renal excretion of corticosteroids and their metabolites can measure steroid output and metabolism over a 24-hour period.


• Aldosterone is a major mineralocorticoid.

• It is Synthesised exclusively in the zona glomerulosa cells.

• It regulates homeostasis of two mineral ions, Na and K, that help regulate blood and volume.

• Aldosterone secretion is controlled by the rennin-angiotensin-aldosterone pathway.

• Dehydration > decrease in blood volume > decrease in BP > stimulation of juxtaglomerular cells in kidneys > increased rennin > liver produces angiotensin > increased angiotensin I > ACE converts angiotensin I to angiotensin II > adrenal cortex produces aldosterone > increased Na and water absorption in kidneys > increased blood volume > increased BP > vasoconstriction of arteries.

• ANP inhibits synthesis and release of aldosterone.

• Some converted in the liver to tetrahydroaldosterone glucuronide

• Some conjugated with glucuronic acid in liver and kidney at 18 oxo-position

• Very little free aldosterone in urine.

• Aldosterone stimulates K secretion in renal tubes.

Adrenocorticoretical Sex Hormones:

• Sex hormones are produced mostly in zona reticularis.

See: FAQ on Adrenal Hormones

ACTH-Cortisol connection:

• ACTH controls secretion of cortisol and adrenal androgens.

• Low dose dexamethasone suppresses pituitary ACTH secretion (and therefore 17-hydroxycorticosteroid production and excretion) in people with a normal pituitary response to the negative feedback action of glucocorticoids.

• Angiotensin II controls secretion of aldosterone.

Regional Adrenal functions:

Zona glomerulosa:

Produces: aldosterone.

Damage results in: Na loss, decreased ECF volume, low BP, circulatory shock, death.

Zona fasciculate and zona reticularis:

Produces: cortisol and androgens.

Damage results in: circulatory failure, inability of release glucose and fatty acids in plasma.


Produces: epinephrine.

Damage results in: inability of release glucose and fatty acids in plasma.

C21 steroids:

• Cortisol; excreted as H2O-soluble metabolites.

C19 steroids:

• Adrenal androgens: DHEA.

• Testosterone.

C18 steroids:

• Estrogens, eg., estradiol.

• Aromatase converts androgens into estrogens.

See: Synthesis and Deficiencies of Adrenal Hormones

Actions of Glucocorticoids:

• These include GH, glucagon, corisol, and epinephrine.

• Released under stress.

• Insulin decreases under stress.

Metabolic Actions of Cortisol:

• Protein degradation, lipolysis, mobilized plasma glucose.

Permissive Actions of Cortisol:

• Enhances activity of glucagon and catecholamines.

Control of ACTH and Cortisol Secretion:

• Stress releases CRH: increased in morning, and decreased during night. ACTH, endorphins released in end.

• ACTH causes release of cortisol; excessive secretion darkens skin - Addison's disease.

• Endorphin: pain modulators.

Cushing Syndrome:

• Secondary hypercortisolism due to pituitary malfunction.

Physiologic Actions of Aldosterone:

Aldosterone tells collecting ducts in kidneys to absorb Na in exchange of K.

Tubule lumen becomes - charged; attracts H+ and K+.

Control of Aldosterone Secretion:

• ACTH stimulates aldosterone secretion.

• Rennin-angiotensin system promotes aldosterone secretion.

• RA system stimulated by sensory cells in juxtaglomerular apparatus; monitor afferent arteriole pressure.

Angiotensin II:

• Secreted due to: low BP, low Na, increased simulation of juxtaglomerular cells.

• Causes: vasoconstriction; increased TPR; release of aldosterone.

Aldosterone Control:

• Increased in hemorrhage, sweating, hyperkalemia, etc.

• Decreased in weightlessness (eg., outer space, water).

Addison's Disease:

• Primary hypoaldosteronism.

• Primary adrenal insufficiency.

• High ACTH and hyperpigmentation.

• Hypotension: decreased glucocorticoids and mineralocorticoids.

• Increased renin and angiotensin.

• Loss of female body hair due to decreased androgens.

• Decreased glucocorticoids, decreased glucose.

• Increased ADH.

Secondary Hyperaldosteronism:

• Blood collects in venous system.

• Decreased CO, BP.

• Caused due to CHF, hepatic cirrhosis, constriction of vena cava.

Additional Readings:

Basic Endocrinology

1. Introduction to Endocrinology
2. Hypothalamic-pituitary system
3. Adrenal Hormones
4. Antidiuretic Hormone (ADH) and ECF Regulation
5. Endocrine Pancreas
6. Growth Hormone
7. Adrenal Medulla
8. Hormonal Control of Calcium and Phosphate
9. Thyroid Hormones
10. Hormones of Male Reproduction
11. Hormones of Female Reproduction
12. Fluid Compartments of the Body
13. Notes on Hypothalamus Anterior Pituitary and Thyroid
14. Additional Notes on Female Reproduction
15. Hormonal Signaling Pathways
16. FAQ on Adrenal Hormones
17. FAQ on Male Reproduction
18. Synthesis and Deficiencies of Adrenal Hormones
19. Significance of Glycosylated Hemoblogin (HbA1c)
20. Significance of Measuring Albumin while with Calcium Levels
21. Stepwise Approach to Treatment of Ascites
22. How to differentiate between Diabetes Insipidus vs Psychogenic Polydipsia

Related Topics

1. Histology of the Endocrine System
2. Histology of the Male Reproductive System
3. Histology of the Female Reproductive System

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