PHYSIOLOGY OF ADRENAL GLAND

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

Zones of adrenal gland

Zones of adrenal gland

Hypothalamo-hypophyseal-adrenal axis

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)***

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 reservoir buffering hormone for use as needed

Steroid & Thyroid Hormones - Mechanism of Action

Figure 74-6; Guyton & Hall

Cholesterol- the precursor of steroid hormones

SYNTHESIS OF ADRENAL STEROID HORMONES

SYNTHESIS OF ADRENAL STEROID HORMONES

FUNCTIONS OF CORTISOL

Cortisol
Helps in resisting stress and inflammation

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)

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

EFFECTS ON LIPID METABOLISM

Mobilizes fatty acids from adipose cells Increases oxidation of fatty acids Helps shift from glucose to fat metabolism during times of starvation or stress Conserves body glucose & glycogen Mobilizes fat from periphery to trunk. Obesity: buffalo torso & round moon face

Antiinflammatory effects of cortisol

Cortisol has three actions that interfere with the body's inflammatory response to trauma and irritants. (1) Cortisol induces the synthesis of lipocortin, an inhibitor of the enzyme phospholipase A2. Phospholipase A2 liberates arachidonic acid from membrane phospholipids and provides the precursor for the prostaglandins and leukotrienes that mediate the inflammatory response. Therefore, this component of the antiinflammatory effect of cortisol is based on inhibiting the synthesis of the precursor to prostaglandins and leukotrienes. (2) Cortisol inhibits the production of interleukin-2 (IL-2) and the proliferation of T lymphocytes. (3) Cortisol inhibits the release of histamine and serotonin from mast cells and platelets.

Anti-inflammatory action of cortisol

Suppression of immune response by cortisol

As previously noted, cortisol inhibits the production of IL-2 and the proliferation of T lymphocytes, which also are critical for cellular immunity. Exogenous glucocorticoids can be administered therapeutically to suppress the immune response and prevent the rejection of transplanted organs. Also used in allergies and in autoimmune diseases. Increased chances of infections

 Maintenance of vascular responsiveness to catecholamines (permissive role of cortisol)

Cortisol is necessary for the maintenance of normal blood pressure and plays a permissive role in the arterioles by up-regulating 1-adrenergic receptors. In this way, cortisol is required for the vasoconstrictive response of the arterioles to catecholamines. In hypocortisolism, there is hypotension; in hypercortisolism, there is hypertension.

 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.

 Increases in glomerular filtration rate (GFR). Cortisol increases GFR by causing vasodilation of afferent arterioles, thereby increasing renal blood flow and GFR.

 Effects on CNS.
Glucocorticoid receptors are found in the brain, particularly in the limbic system. Cortisol decreases REM sleep, increases slowwave sleep, and increases awake time. (Recall that the largest bursts of ACTH and cortisol occur just before awakening at about 8 am.)

Summary of actions of cortisol