Cortisol

Cortisol / Glucocortisol
Ji Keon LOOI

Outline of presentation
This presentation will cover:
•Site of production
•Site of release
•Target organ
•Means of transport
•Action
•Feedback Loop
Of cortisol

To clear things up before we start
•Two major types of adenocorticol hormones – mineralocorticoids and glucocorticoids
•Mineralocorticoids affect the electrolytes (minerals) of the ECF Na+ and K+ in particular
•Glucocorticoids increase blood glucose concentration, effects on CHO, protein and fat metabolism

The glucocorticoids
•Cortisol
•Corticosterones
•Cortisone
•Prednisone
•Methylprednisone
•Dexamethasone

Introduction to CORTISOL
•Principal glucocorticoid, 95% of all GC activity
•Secretion stimulated by ACTH, which in turn is controlled by CRF.
–What are sites of production?
•Produced by adrenal cortex
–Which layers?
•A.k.a stress hormone
•Hydrocortisone (synthetic)

Secretion of adrenocortical hormones by the different zones of the adrenal cortex and secretion of catecholamines by the adrenal medulla. (Diagram from Guyton)

Means of transport & Action
•Cortisol (hydrophobic) travels through the body in the blood via serum globulin.
•It diffuses through the cell membrane.

•Inside the cell, cortisol binds with its protein receptor in the cytoplasm, and the hormone-receptor complex (HRC) then interacts with specific regulatory DNA sequences, called glucocorticoid response elements, to induce or repress gene transcription. (Interaction facilitated by Transcription factors)
•It increases or decreases transcription of many genes to alter synthesis of mRNA for the proteins that mediate their multiple physiologic effects.
•Thus, most of the metabolic effects of cortisol are not immediate but require 45 to 60 minutes for proteins to be synthesized, and up to several hours or days to fully develop.
•N.B.: steroid hormones, exerts its effects by first interacting with intracellular receptors in target cells.

More about the stress hormone…
•Secretion in accordance with circadian rhythm. High in the early morning, low in late evening. Changes in sleeping habits alter the cycles.
–Clinical application: - measurement of blood cortisol only meaningful when expressed in terms of the time in the cycle at which the measurements are made
•Physical/Mental stress enhances secretion of ACTH and consequently cortisol.
•Negative feedback mechanism to decrease CRF and ACTH formation

Effects of Cortisol (1)
CHO metabolism
•Stimulates gluconeogenesis
•Decreases glusoce utilisation by cells
•Elevates blood glucose concentration and “adrenal diabetes”

Protein metabolism
•Reduces cellular protein
•Increases liver and plasma protein
•Increases blood aa, diminishes transport of aa into extrahepatic cells and enhances transport into hepatic cells

Fat Metabolism
•Mobilisation of FACs
•Excess results in obesity

Effects of Cortisol (2)
•Resists stress and inflammation ( )
•Blocks inflammatory response to allergic reactions
Mechanism for regulation of glucocorticoid secretion. ACTH, adrenocorticotropic hormone; CRF, corticotropin-releasing factor.


THE DISORDERS OF CORTISOL SECRETION
Plasma Cortisol Plasma ACTH

Primary Hypercortisolism ↑ ↓
(Cushing Syndrome)

Secondary Hypercortisolism ↑ ↑
(pituitary, Cushing's disease)

Primary Hypocortisolism ↓ ↑
(Addison's disease)

Secondary Hypocortisolism ↓ ↓
(pituitary)

Thank you!!!
Sources
•Guyton, Textbook of Medical Physiology 11th Edn
•Prof. Khalid’s lecture *Components of the Endocrine System*
•http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Adrenals.html