Adrenal physiology

• Adrenal Gland


  Small, triangular glands loosely attached to the kidneys
• Adrenal Gland

  • Divided into two morphologically and distinct regions: Adrenal cortex and Adrenal medulla
• Adrenal Cortical Zones

  • Zona glomerulosa
  • Zona fasciculata
  • Zona reticularis
• Glucocorticoids


  Steroid hormones secreted by the adrenal cortex
• Adrenal Vein Drainage

  • Left adrenal vein drains into renal vein
  • Right adrenal vein drains into IVC
  • Both adrenals have many arteries but only one vein
• Steroids are lipophilic molecules. All steroids, except calcitriol, have cyclopentanoperhydrophenanthrene structure (sterane).
• Steroid Hormone Classes

  • Progestins
  • Glucocorticoids
  • Mineralocorticoids
  • Androgens
  • Estrogens
  • Vitamin D
• Progestins


  The biosynthetic precursors of all other steroid hormones
• Progesterone


  A progestin, produced directly from pregnenolone. Secreted from the corpus luteum. Maintains (with estradiol) the uterine endometrium for implantation. Differentiation factor for mammalian glands.
• Estradiol


  After conversion to dihydrotestosterone, production of sperm proteins in Sertoli cells. Responsible for secondary female sex characteristics. Produced from progesterone.
• Testosterone


  Responsible for secondary male sex characteristics. Produced from progesterone.
• Dehydroepiandrosterone


  Weak androgen, which can be converted to estrogen. Various protective effects. It may play a role in the aging process. Regulates NAD+ coenzymes.
• Cortisol

  Dominant glucocorticoid in humans, synthesized from progesterone in the zona fasciculata of the adrenal cortex. Stress adaptation through various cellular phenotypic expression, stress adaptation. Slight elevation of liver glycogen. Numerous effects on the immune system, killing effect on certain T cells in high doses. Na+ uptake in epithelia lumen.
• Aldosterone


  The principal mineralocorticoid. Produced from progesterone in the zona glomerulosa of adrenal cortex. Causes sodium ion uptake via conductance channel. Occurs in high levels during stress. Rises blood pressure and fluid volume.
• Calcitriol


  Causes synthesis of Ca2+ transport protein. Regulates calcium and phosphorus homeostasis.
• Peptide hormones are encoded by specific genes; steroid hormones are synthesized from the enzymatically modified cholesterol.
• Biosynthesis of Steroid Hormones

  1. Cholesterol is made within the cell from acetyl CoA (de novo synthesis)

  2. Cholesterol is also taken up by the cell in the form of low density lipoprotein (LDL)

  3. Mitochondrial side chain cleavage enzyme cholesterol-desmolase initiates the synthesis of the progestins

  4. Hormone stimulation depends on the cell type and receptor (ACTH for cortisol synthesis, FSH for estradiol synthesis, LH for testosterone synthesis etc.)

  5. Increase in cAMP activates protein kinase whose phosphorylations cause increased hydrolysis of cholesteryl esters from droplet to free cholesterol and increase cholesterol transport into the mitochondrion

  6. Elevated Ca2+ levels and protein phosphorylation bring about induced levels of the side chain cleavage reaction

  7. Steroid is produced, secreted into the extracellular space and circulated to the target tissue in the bloodstream
• Steroidogenic Enzymes

  • Cholesteroldesmolase (Side-chain cleavage enzyme)
  • 3b-hydroxysteroid dehydrogenase
  • 17a-hydroxylase/17,20 lyase
  • 21-hydroxylase
  • 11b-hydroxylase
  • Aldosterone synthase
  • Aromatase
• Zona glomerulosa cells lack the P450c17 that converts pregnenolone and progesterone to their C17 hydroxylated analogs. Thus, the pathways to the glucocorticoids and the androgens are blocked.
• Adrenal Steroid Synthesis

  • Pregnenolone
  • 17-OH pregnenolone
  • dehydroepiandrosterone
  • Progesterone
  • 17-OH progesterone
  • Androstenedione
  • Deoxycorticosterone
  • 11-deoxycortisol
  • 17-b oestradiol
  • Corticosterone
  • Cortisol
  • Aldosterone
• Cortisol


  90-95% bound to plasma protein. Under control primarily by ACTH. There are usually 7-15 episodes of cortisol secretion per day with a major burst in the early morning before awakening.
• Cortisol Transport

  75% bound to cortisol binding globulin (CBG, also known as TRANSCORTIN), 15% bound to albumin, 10% free (unbound) and bioactive
• Stimuli releasing cortisol

  Physical trauma, infection, extreme heat and cold, exercise to the point of exhaustion, extreme mental anxiety, stress
• Physiological effects of cortisol
• Fat metabolism

  • Lipolytic
  • Mobilizes fatty acids & glycerol from adipose tissue leading to↑ their blood concentrations, so more glycerol available for gluconeogenesis
  • Fat broken down & less formed due to less glucose transported into fat cells
  • Redistribution of body fat: ↑ formation of fat in trunk areas & face, ↓ fat (& muscle) from extremities
  • Increases appetite
• Anti-inflammatory effects of cortisol

  • Stabilizes lysosomal membrane
  • Reduces degree of vasodilatation
  • Decreases permeability of capillaries
  • Decreases migration of white blood cells
  • Suppresses immune system
• Effect of cortisol on Blood Cells and Immunity

  • Decrease production of eosinophils and lymphocytes
  • Suppresses lymphoid tissue systemically therefore decrease T cell and antibody production, decreasing immunity
  • This effect is useful in transplantation surgery in reducing organ rejection
• Functions of cortisol - circulation


  • Maintains body fluid volumes & vascular integrity
  • Cortisol has mineralcorticoid effect, not as potent as aldosterone
  • BP regulation & cardiovascular function: sensitizes arterioles to action of noradrenaline (Permissive effect)
  • Decreases capillary permeability
  • Maintains normal renal function
• Functions of cortisol - CNS responses

  • Negative feedback control on release of ACTH
  • Modulates perception & emotion
• Functions of cortisol - Mineral metabolism


  • Anti-vitamin D effect
• Functions of cortisol - GIT

  • Increases HCl secretion
• Developmental Functions of cortisol

  • Permissive regulation of fetal organ maturation
  • Surfactant synthesis (phospholipid that maintains alveolar surface tension)
  • Inhibition of linear growth in children due to direct effects on bone & connective tissue
• During stress, the priorities of the secretions of the hypothalamo-pituitary peripheral-endocrine axes are shifted in favor of the hypothalamo-pituitary-adrenocortical (HPA) axis
• During stress

  • ↑ HPA
  • ↓ GHRH
  • ↓ GH
  • ↓ GnRH
  • ↓ FSH
  • ↓ LH
• Cortisol excess

  • Exogenous (steroid therapy)
  • Endogenous (ACTH-independent, ACTH-dependent)
• Exogenous cortisol excess


  • Most cortisol excess is induced by steroid therapy (prednisone) for asthma, rheumatoid arthritis, lupus, immunosuppression after transplantation
• Endogenous cortisol excess

  • ACTH-independent: Primary adrenal defect (adenoma)
  • ACTH-dependent: Overproduction of ACTH by pituitary, Overproduction of ACTH by ectopic ACTH-producing tumor
• Both exogenous & endogenous hyperfunction show manifestations of Cushing's disease
• Intermediary metabolism effects of cortisol excess

  • Carbohydrate metabolism: ↑ blood glucose levels, ↓ sensitivity to insulin
  • Protein metabolism: ↑ protein loss, muscle atrophy, thin skin, bone matrix & mass losses; bone formation ↓, less Ca2+ absorbed & more excreted in urine, osteoporosis
  • Fat metabolism: redistribution of body fat: ↑trunk & face fat deposition & ↓ extremities fat deposition
• Circulatory effects of cortisol excess

  • Hypertension due to Na retention & K excretion
  • Hypervolemia
  • Hypernatremia due to increased Na absorption
  • Hypokalemia due to increased K excretion