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Biosynthesis and regulations of adrenal cortex hormones

Adrenal glands: lie at the superior poles of the two kidneys.

Composed of the adrenal medulla and the adrenal cortex.

  • The adrenal cortex is the outer portion constituting 80% to 85% of its total mass.
  • The inner central portion of the gland is the adrenal medulla constituting 15% to 20% of the total mass of the gland.

The adrenal cortex consists of 3 morphologically distinct zones.
These zones differ in histological and ultrastructural morphology, enzymatic content, and functional activity.
The 3 layers are :
Zona Glomerulosa
Zona Fasciculata and
Zona Reticularis

Adrenal cortex layer and secretion of different hormones

Zona Glomerulosa

  • Outer sub capsular layer.
  • Constitutes about 15 per cent of the adrenal cortex.
  • This zone secretes mineralocorticoids
  • secretes aldosterone.
  • Contain the enzyme aldosterone synthase

Zona Fasciculata

  • Is the middle layer.
  • Constitutes about 75 per cent of the adrenal cortex
  • This secretes mostly Glucocorticoids (cortisol) and to slight extent sex hormones (androgens and estrogens).
  • The secretion of these cells is controlled by adrenocorticotropic hormone (ACTH).

Zona Reticularis

  • Is the innermost layer.
  • This zone secretes mostly sex hormones and to a slight extent glucocorticoids

Synthesis of Adrenocortical Hormones Are Steroids Derived from Cholesterol

Synthesis of adrenal cortex hormone using mitochondria. pic source: Berne and Levy Physiology,6th edition
  • All human steroid hormones are synthesized from cholesterol.
  • Cholesterol is made available from two sources: i) from blood and ii) synthesized de novo.
  • Low-density lipoproteins provide 80 percent of the cholesterol used for steroid synthesis
  • LDL diffuses from the plasma into the interstitial fluid and attaches to specific receptors called coated pits on the adrenocortical cell membranes.
  • The formation of the important steroid products of the adrenal cortex:
  • aldosterone, cortisol, and the androgens.
  • Essentially all these steps occur in two of the organelles of the cell mitochondria and the endoplasmic reticulum
  • Each step is catalyzed by a specific enzyme system shown in the diagram below.
Biosynthesis of adrenal cortex hormone using different enzymes.


  • Aldosterone (very potent)
  • Desoxycorticosterone (1/30 as potent as aldosterone, but very small quantities secreted)
  • Corticosterone (slight mineralocorticoid activity)
  • 9a-Fluorocortisol (synthetic, slightly more potent than aldosterone

Regulation of Aldosterone Secretion

  • Regulated by: angiotensin II, ACTH, and plasma K+ concentration. An increase in potassium is the most potent stimulus for aldosterone.
  • Angiotensin II acts through binding with the AT1 receptor present in zona glomerulosa cells and increasing intracellular IP3 and DAG-increase intracellular calcium-increase aldosterone secretion and synthesis.
  • ACTH acts through ACTH receptor mediated by cAMP and protein kinase
    • Increased K+ concentration in ECF activates voltage-gated Ca2+ channels and increases intracellular calcium-increase aldosterone secretion and synthesis.


  • Cortisol (very potent, accounts for about 95 percent of all glucocorticoid activity)
  • Corticosterone (provides about 4 percent of total glucocorticoid activity, but is much less potent than cortisol)
  • Cortisone (synthetic, almost as potent as cortisol)
  • Prednisone (synthetic, four times as powerful as cortisol)
  • Methylprednisone (synthetic, five times as powerful as cortisol)
  • Dexamethasone (synthetic, 30 times as potent as cortisol

Adrenal androgens

  • Dehydropeiandrosterone and androstenedione. • Converts into testosterone in target tissues.
  • In males causes early development of male sex organs. • Androgens have a role in females too.
  • Adrenal androgens can be converted into estrogen in adipose tissues.

Regulation of cortisol and androgen

Note: An increase in androgen level have no inhibitory effect in the hypothalamus and pituitary, whereas an increase in cortical has an inhibitory effect. therefore in some clinical conditions to decrease the effect of ACTH hormones, cortisol is given.

Regulation of cortisol and androgen. Pic source: Berne and Levy Physiology, 6th edition


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