Dr.

Farrukh Majeed
Department of Physiology
Endocrinology lecture-9
Glucocorticoids
 Learning objectives
At the end of this lecture student should be able
to:
• Explain regulation and functions of
glucocorticoids.
• Determine diseases produced by
increase/decrease Cortisol hormone.
 Case scenario: Fatima is very sick
• Fatimah, 35 year old female presents with general muscle weakness and low
back pain since 4 months. She says lately she has little interest in her regular
activities and has been experiencing fatigue without physical exertion.
• Patient was diagnosed with type II Diabetes in her late 20’s and has been
taking insulin regularly since her diagnosis.
• Previously for hip pain secondary to bursitis, her primary care physician
administered multiple corticosteroid injections. In addition patient also reports
taking inhaled corticosteroids for the past 7 years.
• She has irregular menstrual cycles for the past 2 years accompanied by
unexplained weight gain in her abdomen
Upon physical examination:
• purple/pink stretch marks on arms, abdomen, and thighs. Pt has multiple cuts
and bruises on her arms and hands with an explanation of having thin skin. Pt
is obese with noticeable fatty deposits in the upper back and midsection.
• Identify possible hormonal imbalance.
• Identify possible cause for development of this
disease in this patient.
• which hormonal test you can advice to confirm
your diagnosis?
• Explain pathophysiology of her sign/symptoms.
 Glucocorticoid
• At least 95 %of the glucocorticoid activity of
the adrenocortical secretions cortisol,
known also as hydrocortisone.
• small but significant amount of glucocorticoid
activity is provided by corticosterone.
Cortisol-Mechanism of Action
 Regulation of Cortisol secretion
Different types of stress that increase
cortisol release are the following:
1. Trauma of almost any type
2. Infection
3. Intense heat or cold
4. Injection of norepinephrine and other
sympathomimetic drugs
5. Surgery
6. Injection of necrotizing substances
beneath the skin
7. Restraining an animal so that it cannot
move
8. Almost any debilitating disease
Functions of Cortisol
 Cortisol-metabolism
• The overall effect of cortisol’s metabolic
actions
• increase the concentration of blood glucose at
the expense of protein and fat stores.
 Cortisol: Carbohydrate Metabolisms
• It stimulates hepatic (liver) gluconeogenesis Between
meals or during periods of fasting.
• The glycogen (stored glucose) in the liver tends to become
depleted broken down to release glucose into the blood.
• Cortisol inhibits glucose uptake and use  many tissues, but
not the brain, thus sparing glucose for use by the brain,
• The rise in blood glucose insulin here insulin not as
effective in maintaining plasma glucose as they are under
normal condition “Adrenal Diabetes”
 Cortisol: Protein Metabolism
• It stimulates protein degradation in many
tissues, especially muscle.
• Breaking down a portion of muscle proteins
severe muscle weakness increase Blood
amino acids.
• Amino acids 
– Gluconeogenesis
– protein synthesis in the liver
– formation of plasma proteins by the liver,
 Cortisol: Fat Metabolism
• Lipolysis of adipose tissue increases
free fatty acids in the plasma
increases their utilization for energy.
• Obesity 
– Many people with increase cortisol
secretion exhibit  excess deposition of fat
in the chest and head regions of the body,
giving a buffalo-like torso and a rounded
“moon face.”
– Excess stimulation of food intake with fat
being generated in some tissues of the
body more rapidly than it is mobilized and
oxidized
 Cortisol: Permissive Actions
• Cortisol is extremely important for its
permissiveness. (enhance other hormonal action)
• For example, cortisol must be present in adequate
amounts to permit the catecholamines to induce
vasoconstriction (blood vessel narrowing).
• A person lacking cortisol, if untreated, may go into
circulatory shock in a stressful situation that
demands immediate widespread vasoconstriction.
 Cortisol: Adaptation to Stress
• Stress major stimulus for cortisol secretion.
• Mechanism
A primitive human or an animal wounded or faced
with a life-threatening situation must forgo eating.
increased availability of blood glucose would help
protect the brain from malnutrition during the imposed
fasting period.  Also, the amino acids  protein
degradation  supply of building blocks for tissue
repair if physical injury.
 Cortisol: Anti-inflammatory effect
Cortisol has two basic anti inflammatory effects:
(1) it can block the early stages of the
inflammation process before inflammation
even begins, or
(2) if inflammation has already begun, it causes
rapid resolution of the inflammation and
increased rapidity of healing.
1) Cortisol Prevents the Development of Inflammation:
• stabilizes the lysosomal membranes reduced release of proteolytic enzymes
• decreases the permeability of the capillaries  prevents loss of plasma.
• decreases both migration of white blood cells into the inflamed area and
phagocytosis of the damaged cells  decrease prostaglandins and leukotrienes
• suppresses the immune system  decrease lymphocyte production  reduced
amounts of T cells and antibodies in the inflamed area lessen the tissue
reactions.
• reduces fever  reduces the release of interleukin-1  reduces the degree of
vasodilation.
2) Cortisol Causes Resolution of Inflammation. cortisol
can often reduce inflammation within hours to a few days.
– The immediate effect is to block most of the factors that are
promoting the inflammation.
– the rate of healing is enhanced
– mobilization of amino acids used to repair the damaged
tissues
– increased glucogenesis that makes extra glucose available in
critical metabolic systems
– increased amounts of fatty acids available for cellular energy
– inactivating or removing inflammatory products.
Cortisol: Blocks Inflammatory Response to
Allergic Reactions
• Administration of cortisol, followed by its effect in
reducing inflammation and the release of
inflammatory products, can be lifesaving.
• For instance, cortisol effectively prevents shock or
death in anaphylaxis
 Cortisol: Blood Cells and on Immunity in Infectious Diseases.

• Cortisol decreases the  eosinophils and lymphocytes

• Administration of large doses of cortisol  atrophy of all the lymphoid
tissue throughout the body,  decreases T cells and antibodies from the
lymphoid tissue. the level of immunity for almost all foreign invaders
of the body is decreased
• This can lead to fulminating infection and death from diseases that would
otherwise not be lethal.
• Cortisol used preventing immunological rejection of transplanted
hearts, kidneys, and other tissues.
• Cortisol increases the production of red blood cells polycythemia often
•  unknown reason.
Diurnal variation in cortisol secretion
 Abnormal cortisol secretion
Excessive cortisol secretion: Primary adrenocortical
CUSHING’S SYNDROME insufficiency
 Reading material
• Guyton 11th edition, 950-955.
• Sherwood 9th edition, page no, 674- 675.