1. Adrenal cortical Hormones – Glucocorticoids/Cortisole Lecture NO: - 2nd MBBS
Dr Muhammad Ramzan

2. Adrenal/supra renal Gland
It Is an endocrine gland situated at the upper pole of both kidneys - Right and left
Is semi lunar in shape consisting of 2 distinct parts:
the adrenal medulla and Cortex
Its cortex secretes steroid hormones . Major 3 : Aldosterone, Cortisole, and Androgens
Adrenal medulla secretes epinephrine and nor epinephrine

3. Adrenal Cortex – the histology
Adrenal cortex comprises of 3 zones going from outside to inside and produce:
Zona Glomeruloza = Minerolocorticoid - Aldosterone
Zona Fasciculata = Glucorticoids Cortisole
Zona Reticularis = Androgens Testosterone

4. Adrenal gland- Histology

5. Cortisole – the definition
Cortisole is a steroid hormone secreted by the Zona Fasciculata of the adrenal cortex
A Glucocoticoid that derives its name from its association with glucose metabolism
Its secretion from the adrenal cortex and
Steroidal nature

6. Cortisole – the background
Regulates blood glucose level and metabolism
Controls the salt water balance and BP
Excess promotes weight gain in face, chest and abdomen
Slender arms, legs and central obesity
Cortisole is Known to suppress; Immunity, autoimmune diseases and Inflammation
Acts as a stress hormone

7. Properties of Cortisole
CH is the precursor for all steroid hormones
Cortisole is Water soluble and exists in free and bound form
Bound form are transported in the blood in combination with the plasma proteins – Albumen and Globulin
Albumen is the common plasma protein carrier
Globulin is the specific carrier protein for Cortisole

8. Cortisole - Biosynthesis
CH is the primary precursor for the synthesis of Cortisole and takes place in the SER of Zona Fasciculata
CH is converted to Pregnenolone and Progesterone and further to 17 α Hydroxy progesterone and Deoxycortisole
Deoxycortisole is altered to Cortisole
Major enzyme involved is the Cytochrome 450

9. Cortisole Biosynthesis

10. Target organs for Cortisole
Target organs are the ones with Cortisole receptors. Are different from other steroids (GCR- GPCR)
All the animal cells have Cortisole receptors
Major ones are the : Liver; Adipose tissues, muscles
CNS : Hypothalamus and anterior pituitary gland
CVS: Cardiac and vascular smooth muscles
Immune system; B,T lymphocytes and Plasma cells

11. Cortisole – the Regulation
Cortisole is regulated through – negative feed back
It is achieved by 2 pathways
1. Neuroendocrine/Long loop/Indirect pathway
Short loop/direct pathway

12. Neuroendocrine/long loop pathway
Hypothalamic – Pituitary – Adrenal- axis
This is the interaction B/W circulating level of Cortisole and Corticotrophin Releasing hormone (CRH) from the hypothalamus
The deficiency of Cortisole ↑the hypothalamic CRH leading to the ↑ the ACTH from Pituitary to ↑Cortisole from Adrenal Cortex
Opposite is true when Cortisole is high

13. Short loop / Direct pathway
Pituitary – Adrenal- Cortisole axis
This is the interaction B/w circulating level of Cortisole and
ACTH from anterior pituitary gland
Deficiency of Cortisole leads to ↑ the ACTH from the Pituitary and Cortisole from Adrenal cortex
Opposite is true when Cortisole is high

14. Regulation of Cortisone

15. Cortisole - Mechanism of action activation of genes
Cortisole is a steroid and its mechanism of action is similar to the rest of the steroids (activation of genes)
Cortisole binds with the Cytoplasmic receptors to form HRC that is translocated to the
Acceptor site at Nucleus to form HRE - the gene
Transcription of mRNA leads to the expression of Protein/Enzymes that carry out Cortisole action

16. Mechanism of action of Cortisole

17. Metabolic effects of Glucorticoids
Cortisole affect all the body cells as most of them have steroid receptors
Major metabolic effects of Cortisole are on :
Protein metabolism
Lipid metabolism
Carbohydrate metabolism
Immune system and development of lungs

18. Effects on protein metabolism
Cortisole promotes Proteolysis to divert amino acids for hepatic Gluconeogenesis
AAs are mobilized from the breakdown of extra hepatic tissues like Skeletal muscles to ↑ AAs level
Free AAs are prevented from their entry into the cell and inhibits Proteogenesis

19. Metabolic effects on lipid metabolism
Cortisole stimulates the break down of fats/lipolysis in adipose tissue and Releases:
Glycerol, free fatty acids and elevates their level in blood and satisfies energy needs of the body
Glycerol is used for Gluneogenesis

20. Effects on carbohydrate metabolism
Cortisole inhibits glucose uptake by extra hepatic tissues like : the muscles and adipose tissues
Inhibits Glycolysis,↑ blood glucose level – is hyperglycemic
Cortisole ↑ Gluconeogenesis by ↑ the enzymes involved
The AAS are released by the Proteolysis of the skeletal muscles of the body

21. Effects on Immune system
Cortisole has potent anti-inflammatory and immuno- -suppressive properties.
This is particularly evident when they are administered at pharmacologic doses
Consequently, Cortisole is widely used as :
drugs for the treatment of allergies; hypersensitivity and Auto Immune diseases like Rheumatic fever/ arthritis, Glomerunephritis and graft rejection

22. Effects on immune systems- the mechanism
Cortisole suppresses the immune system by:
Muting the white blood cells 1
Reduces the their production from the bone marrow
Inhibits IgA secretion in serum
Reduces Collagen fiber synthesis and wound repair

23. Effects on the development of Lungs
Cortisole is essential for the maturation and function of the lungs especially in premature infants
This is due to the synthesis of Surfactant , a molecule essential to prevent the collapse of the lungs
Also called as Respiratory distress syndrome
Cortisole is given to the expectant mothers to prevent the deficiency of surfactant in premature infants

24. Abnormalities of Cortisole production
It is the ability of adrenal gland to produce its hormones that are either too high or too low for the body requirements
Cortisole is secreted either in excess or there may be deficiency of Cortisole
Excess of Cortisole is called Cushing's syndrome
Deficiency is referred to Addison disease

25. Excess – Cushing's Syndrome
is a metabolic disorder caused by the excess of the Cortisole from the adrenal cortex
It is associated with obesity, DM and hypertension
Causes are : Exogenous and endogenous
Exogenous : Long term use of oral Cortisole
Endogenous: Pituitary/Adrenal adenomas/ectopic tumours

26. Features of Cushing's syndrome
It is common in adults and women
Obesity, hypertension and diabetes mellitus
Buffalo hump – A fatty mass B/W the shoulders
Slender legs and arms
Rounded moon like faces
Purple/Pink stretch marks over the abdomen; chest thighs and arms. Skin is thin and easily bruise able

27. Diagnosis of Cushing syndrome
Comparison of old and fresh photographs
24 hour urine collection for the Cortisole estimation
Low dose (1mg) Dexamethasone suppression test:
1mg Dexamethasone, dose at 11PM and blood Cortisole estimation at 8AM of the following morning
Low level of Cortisole suggestive of Cushing disease
Network Association

28. Cushing's syndrome – Central obesity

29. Moon like face with Facial plethora

30. Buffalo hump

31. SKIN stretches

32. Deficiency of Cortisole - Addison's' disease A British physician
It is an endocrine disorder in which adrenal glands produce less steroids than body requirements
Major cause is the auto immune disease of the adrenals
May be associated with Aldosterone deficiency
Characterized by the weight loss; muscle wasting, hypotension
Hypoglycemia, Abdominal pain and vomiting

33. Diagnosis of Addison disease
blood examination reveals :
Low sodium, Cortisole and ACTH
Elevated Potassium and

34. Feature of Addison's disease

35. Addison's disease – John F. Kennedy

36. Addison disease

37. Hyper pigmentation in Addison disease