1st Lecture on the Physiology of Adrenal Gland by Dr Roomi

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PHYSIOLOGY OF

ADRENAL GLAND

By

Dr. Mudassar Ali Roomi (MBBS, M.Phil.)

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Zones of adrenal gland

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Zones of adrenal gland

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Hypothalamo-hypophyseal-adrenal axis

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Glucocorticoids

Cortisol (95% of g.c. activity)

Corticosterone (4% of g.c. activity)

Synthetics (potency) Cortisone (1X cortisol)

Prednisone (4X cortisol)

Methylprednisone (5X cortisol)

Dexamethasone (30X cortisol)***

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Plasma proteins binding

Adrenalcortical hormones bind to

Cortisol-binding globulin (transcortin)

Albumin

Bound cortisol 90 to 95% long half life (60 to 90 minutes)

Free aldosterone 40%

short half life (20 minutes)

Bound hormone serves as a reservoirbuffering hormone for use as needed

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Steroid & Thyroid Hormones - Mechanism of Action

Figure 74-6; Guyton & Hall

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Cholesterol- the precursor of steroid hormones

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SYNTHESIS OF

ADRENAL STEROID

HORMONES

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SYNTHESIS OF ADRENAL STEROID HORMONES

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FUNCTIONS OF CORTISOL

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Cortisol

Helps in resisting stress and inflammation

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EFFECTS ON CARBOHYDATRE METABOLISM

Gluconeogenesis

enzymes to convert a.a. glucose

mobilization of a.a. from extrahepatic tissue

Mainly from muscles

glycogen storage in liver

glucose utilization by cells (insulin resistance)

blood glucose (adrenal diabetes)

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EFFECTS ON PROTEIN METABOLISM

Reduces protein stores in almost all cells

decreased protein synthesis

increased catabolism of protein (causes weakness

of muscles) EXCEPT in liver cells

Increases liver & plasma proteins

Increases blood amino acids Decreases transport into extrahepatic cells

Increases transport into hepatic cells

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EFFECTS ON LIPID METABOLISM

Mobilizes fatty acids from adipose cells

Increases oxidation of fatty acids

Helps shift from glucose to fat metabolismduring times of starvation or stress

Conserves body glucose & glycogen

Mobilizes fat from periphery to trunk. Obesity: buffalo torso & round moon face

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Antiinflammatory effects of cortisol

Cortisol has three actions that interfere with the body'sinflammatory response to trauma and irritants. (1) Cortisolinduces the synthesis oflipocortin, an inhibitor of theenzyme phospholipase A2. Phospholipase A2 liberatesarachidonic acid from membrane phospholipids and

provides the precursor for the prostaglandins andleukotrienes that mediate the inflammatory response.Therefore, this component of the antiinflammatory effectof cortisol is based on inhibiting the synthesis of theprecursor to prostaglandins and leukotrienes.

(2) Cortisol inhibits the production ofinterleukin-2 (IL-2)and the proliferation of T lymphocytes.

(3) Cortisol inhibits the release ofhistamine and serotoninfrom mast cells and platelets.

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Anti-inflammatory action of cortisol

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Suppression of immune response by cortisol

As previously noted, cortisol inhibits theproduction of IL-2 and the proliferation of Tlymphocytes, which also are critical for cellularimmunity.

Exogenous glucocorticoids can be administeredtherapeutically to suppress the immune responseand prevent the rejection of transplanted organs.Also used in allergies and in autoimmune

diseases.

Increased chances of infections

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Maintenance of vascular responsiveness tocatecholamines (permissive role of cortisol)

Cortisol is necessary for the maintenance of

normal blood pressure and plays a permissive rolein the arterioles by up-regulating 1-adrenergicreceptors. In this way, cortisol is required for thevasoconstrictive response of the arterioles to

catecholamines. In hypocortisolism, there is hypotension;

in hypercortisolism, there is hypertension.

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Inhibition of bone formation.

Cortisol inhibits bone formation by:

decreasing the synthesis of type I collagen, the

major component of bone matrix;

by decreasing osteoblast production;

and by decreasing intestinal Ca2+ absorption.

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Increases in glomerular filtration rate (GFR).

Cortisol increases GFR by causing vasodilation

of afferent arterioles, thereby increasing renal

blood flow and GFR.

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Effects on CNS.

Glucocorticoid receptors are found in the brain,

particularly in the limbic system.

Cortisol decreases REM sleep, increases slow-

wave sleep, and increases awake time. (Recall that

the largest bursts of ACTH and cortisol occur just

before awakening at about 8 am.)

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Summary of actions of cortisol

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