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GLUCOCORTICOIDS

Glucocorticoids are a class of corticosteroids secreted from Zona fasciculata from the adrenal cortex.

GLUCOCORTICOIDS

Glucocorticoids are a class of corticosteroids secreted from Zona fasciculata from the adrenal cortex.

The zona fasciculata (sometimes, fascicular or fasciculate zone) is the middle and widest zone of the adrenal cortex, situated directly beneath the zona glomerulosa, and its Constituent cells are organized into bundles or "fascicles".

1946, Edward Calvin Kendall isolated four steroidal compounds from adrenal extracts, which he named compounds A, B, E, and F, Compound E would become known as cortisol and was synthesized later that year by Sarett.

Glucocorticoids are catabolic hormones that are released during stress.

Glucocorticoids are cholesterol-derived steroid hormones and so are lipid- soluble so they have to transport around the blood bounded by carrier protein known as transcourtin.

Glucocorticoids include: 1. cortisol (95%) 2. corticosterone

Synthetic steroids are cortisone (potent as cortisol) prednisone (4 times as cortisol), and dexamethasone (30times as cortisol).

Glucocorticoids can syntheticaly made and injected or taken orally.

Some sports people use cortisol to relieve pain quickly for a duration of time.

Taking corticoids for a long time has some very bad effects

Cortisol:

Cortisol is a steroid hormone in the glucocorticoid class of hormones and helps your body to respond to stress including the stress of illness, injury or surgery. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the zona fasciculata of the adrenal cortex in the adrenal gland. It is produced in other tissues in lower quantities. It also maintains blood pressure, heart function, immune system and blood glucose level ( as the main function of cortisol is to increase blood glucose level).

Its synthesis: 1.Cholesterol transport via StAR and pregnenolone synthesis by CYP11A1

Conversion of pregnenolone to progesterone

Progesterone to 17-alpha-hydroxyprogesterone17-alpha-hydroxyprogesterone to 11deoxycortisol

Conversion of 11-deoxycortisol to cortisol.

2.Cortisol structure: Cortisol is a 17alpha-hydroxy-C21-steroid that is pregn-4-ene substituted by oxo groups at positions 3 and 20 and hydroxy groups at positions 11, 17 and 21.

Functions of glucocorticoids:

A-Permessive action (low level of cortisol).

B-Physiological action (Normal level of cortisol).

C-Pharmacological action ( high level of cortisol).

A. permessive action:

Permissive actions, identified and elucidated by Dwight Ingle; are those by which glucocorticoids at basal levels permit or normalize responses to stress and various agents, including other hormones, by priming some of the body's homeo- static defense mechanisms.

It's represented in:

1- Glucocorticoids must be present for catecholamines to exert their gluconeogenic, lipolytic effects, vasoconstriction and bronchodilatation.

2- Glucocorticoids must be present for glucagon to exert their

gluconeogenic and lipolytic effects.

3 - Glucocorticoids must be present for angiotensin II to produce vasoconstriction.

B. physiological action:

I. effect on metabolism: Glucocorticoids have a pivotal role in the glucose, protein, and fat metabolism of the body represented in:

1. Carbohydrates metabolism:

(1) It stimulates gluconeogenesis (synthesis of new glucose) in liver cells.

Mechanism: 1. stimulate extra-hepatic protein catabolism.

                         2. increase amino acid uptake by hepatic cells. 



                          3. increase activity of hepatic transaminases which convert amino to ketoacids.  4. then ketoacids enter the pathway of conversion to glucose.  

(2) It Stimulates glycogenesis, i.e.: 1 increase liver glycogen because of increase gluconeogenesis.

(3) It Increases glucose release from the liver.

(4) It decreases glucose utilization by liver, muscle, and adipose tissue and peripheral tissue (except heart and brain).

All these actions may lead to hyperglycemia and produce diabetic type of glucose tolerance curve in individuals with genetic predisposition to diabetes (adrenal diabetes).

2.Protein metabolism:

In extra-hepatic tissue, they are catabolic, in intra-hepatic tissue they are anabolic.

In extra-hepatic tissue, cortisol reduces protein stores (especially muscle& adipose tissue) by decreasing protein synthesis and increasing protein catabolism.

In intra-hepatic tissue: 1. Increase >protein synthesis
2.Increase-> plasma protein
3.Increase >gluconeogenesis

3. Fat metabolism:

1-Cortisol has a lipolytic action:

(a) It mobilizes fatty acids from adipose tissue.

(b) Itactivates a hormone sensitive lipase enzyme in fat cells.

2-Increase free fatty acids (FAA) in plasma. These FFA are utilized as a source of energy.

3- Cortisol is ketogenic (increases ketone body).

4-Decrease hepatic lipogenesis.

5-Excess dose: stimulates lipogenesis in some tissues & promotes deposition& redistribution of fat in face, back of neck & trunk & abdomen.

II. Effect on appetite:

1. 
   

   Cortisol increases appetite by inducing neuropeptide Y in hypothalamus& decreasing corticotropin releasing hormone (CRH)

   
   


2. 
   

   Cortisol induces leptin synthesis in adipocytes ---> which exert negative feedback on appetite center.

   
   

III. Effect on muscle:

1. 
   

   It maintains skeletal muscle contraction via increase acetylcholine.

   
   


2. 
   

   It has inotropic action on cardiac muscle, increase Na*-K* ATPase & B-adrenergic receptors.

   
   

IV. Effect on vascular system:

maintenance of normal arterial blood pressure:

(1)It maintains myocardial contractility.

(2) decreases production of vasodilator prostaglandins.

(3) decreases permeability of vascular endothelium.