Glucocorticoids – Functions & Regulation

GLUCOCORTICOIDS – FUNCTIONS & REGULATION

Adrenal glands:

• Paired structures situated above kidney.
• Layers – Outer cortex & inner medulla.
• Adrenal cortex is essential for life.

Adrenal cortex:

• Contains 3 layers

Secretions:

• Corticosteroid hormones – Glucocorticoid, mineralocorticoids & androgens

Glucocorticoids:

• All act on intracellular cytoplasmic receptors

Functions:

• Important effects on multiple organ systems, mostly are permissive.
• Primary role – Help body cope with acute or chronic stress 
• To execute “Fight” / “Flight” response

Important actions of glucocorticoid:

1. Carbohydrate metabolism – 

• Promote gluconeogenesis & glycogenesis in liver.
• Reduce peripheral utilization of glucose in most tissues except “Brain & Heart”.

Facilitating action:

• Presence of cortisol – Glucagon & adrenaline is more effective in producing muscle glycogenolysis.
• Combined result,
• Increased blood glucose level.
• Improved glucose supply to Brain & Heart in stress.

2. Protein metabolism – 

• Both catabolic (in muscles) & anabolic (in liver) effects.

In muscle –

• Inhibits protein synthesis
• Enhances protein breakdown (proteolysis)

In Liver –

• Anabolic effect 
• Increases synthesis of enzymes involved in hepatic proteins production.

Overall effect –

• Anti-anabolic (catabolism).
• Hence, excess cortisol (Cushing syndrome) causes negative nitrogen balance

3. Fat metabolism –

• Cortisol promotes lipolysis directly & also indirectly (permissive action).
  • By enhancing lipolysis caused by glucagon, GH, adrenaline & thyroxine
• FFA level is increased due to lipolysis.
  • Fuel during stress & starvation.

4. Cardiovascular effects – 

• Cortisol needs maintainance for normal vascular integrity & responsiveness.
• Enhances vascular responsiveness to norepinephrine
• Hence maintaining normal BP & volume

5. Effect on blood cells – 

• Stimulates hemopoiesis & increases no. of circulating erythrocytes, neutrophils & platelets.
• Reduces no. of circulating lymphocytes, eosinophils & basophils.
  • By promoting tissue migration.

6. Renal effects – 

• Glucocorticoids facilitate rapid excretion of water load (increase free-water clearance)
• Enhance uric acid excretion.

Note:

• Mineralocorticoids does not have these effects.
• So, glucocorticoids maintain normal GFR not aldosterone.

7. Gastric effects – 

• Increases gastric acid secretion.
• Decrease gastric mucosal cell proliferation
• Hence, corticosteroids predispose to peptic ulceration. 

8. Muscle contraction – 

• Optimism level of glucocorticoids is needed for normal muscular activity.
• By increasing contraction force helpful in stress.

9. Stress adaptation – 

• Stress increases ACTH secretion→ Increased glucocorticoid secretion.
• Glucocorticoids help to cope up stress

10. Anti-growth effects – 

• Large doses of cortisol decrease Ca²⁺absorption from gut & enhance its renal excretion.
• Inhibits mitosis of fibroblast.
  • Increase degradation of collagen.
  • Leads to osteoporosis & delayed wound healing.

11. Other effects – 

Anti-inflammatory – 

• Corticosteroids induce production of lipocortins 
• Results phospholipase A₂ inhibition.
• An enzyme involved in production of inflammatory mediators (PGs, LTs, PAF)
• Immunosuppressive.
• Anti-allergic.
• Psychological effects.

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