Cortisol- Synthesis, Regulation, Physiological actions, Disorders I Adrenal I Endocrine Physiology This video will be about the following 1. Cortisol 2. Synthesis 3. Regulation 4. Mechanism of action 5. Physiological action 6. Clearance 7. Disorders You can also watch the same topic on HM Learnings Youtube channel. You can also follow HM Learnings on facebook, instagram and twitter for daily updates

2. Cortisol
• Steroid hormone
• Stress hormone
• It is a primary glucocorticoid which is synthesized and secreted by zona
fasciculata layer of adrenal cortex.
• After release, majority of it will bind to corticosteroid binding globulin
(transcortin) and some to albumin or in free form in plasma.

3. Synthesis of cortisol

4. Cholesterol
Pregnenolone
17 hydroxy
progesterone
17 hydroxy pregnenolone
Progesterone 11 deoxy corticosterone
11 deoxy cortisol
Corticosterone
Cortisol
SCC
17 α hydroxylase 17 α hydroxylase
17 α hydroxylase 17 α hydroxylase
3β
HSD
21α
hydroxylase
11β
hydroxylase

5. Regulation- HPA axis

6. Diurnal rhythm

7. Action of ACTH

8. Action of ACTH
ACTH will increase the synthesis of :
A. SCC enzyme (rate limiting enzyme in steroid hormone synthesis)
B. LDL receptor mediated uptake of cholesterol
C. HMG-CoA reductase (rate limiting enzyme in cholesterol synthesis)

9. Mechanism of action of cortisol

10. Mechanism of action of cortisol
Cortisol cross the plasma membrane
Bind to nuclear receptor
Bind to cytoplasmic receptor
Detachment of receptor from hsp90 and exposure
of nuclear localization signal
Cortisol- GR receptor complex
translocate to the nucleus
Bind to glucocorticoid response element
Induce gene transcription
Protein synthesis to bring the
biological effect
Dimerization of cortisol-GR complex

11. Physiological action
• Metabolic actions

12. Anti-inflammatory &
immunosuppressive action

13. Effect on cardiovascular system
• Permissive action of cortisol increase the response of adrenergic receptor to
circulating catecholamines.
• Cortisol increase the expression and responsiveness of adrenergic receptors
and hence increase the BP and CO.
• Effect on blood cells
• Cause neutrophilia, monocytosis, eosinopenia, basopenia, lymphocytopenia
• Effect on connective tissue
• Decrease the fibroblast proliferation and collagen formation.
• Bruising occurs

14. Effect on CNS
• Mood and behavior
• Decrease REM sleep
• Effect on GIT
• Increase acid secretion, gastric ulcer
• Effect on bone
• Decrease Ca2+ absorption and reabsorption and also inhibit the
osteoblast , thus osteopenia/osteoporosis.
• Effect on fetus
• normal development of the CNS, retina, skin, GI tract, and lungs.
• Surfactant formation in lungs

15. Clearance of cortisol
• Done by kidney and liver.
• These organs have 11β hydroxysteroid dehydrogenase convert cortisol
to cortisone (inactive), followed by its removal.

16. Disorders
• Cushing’s syndrome- Constellation of clinical features that result from
chronic exposure to excess glucocorticoids of any etiology.
• Causes- ACTH producing pituitary tumor, ectopic tumor,
adrenocortical adenoma
Addison’s disease- Deficient production of glucocorticoid due to adrenal
insufficiency.
Causes- autoimmune adrenal disease, genetic disorders