THE ADRENAL GLAND

Dr. Ayisha Qureshi

Assistant Professor,
MBBS, Mphil
 THE ADRENAL
GLANDS
• 2 in number
• Each weighs about 4 gms.
• They are located above the
upper pole of each kidney
in the retroperitoneal space.
• Each adrenal is composed
of 2 distinct parts:
- Adrenal cortex
- Adrenal medulla
• Embryologically, the cortex
is derived from the
mesoderm whereas the
medulla is derived from the
neural crest cells that
migrate into the developing
cortex.
 Each Adrenal Gland consists of a STEROID-SECRETING CORTEX and a
CATECHOLAMINE-SECRETING MEDULLA.
On the basis of their primary action, the adrenal steroids (the
adrenocortical hormones) can be categorized into:
•Mineralocorticoids
•Glucocorticoids
•Sex Hormones esp. Androgens
PROPERTIES
Adrenocortical hormones
BIOSYNTHESIS OF
ADRENOCORTICAL
HORMONES
LDL-Receptor Mediated Transport
What happens when there is a deficiency of
the enzyme 21 α-Hydroxylase Deficiency?
From the last slide we can predict that deficiency of this enzyme will
lead to inadequate production of both glucocorticoid and
mineralocorticoid hormones.
Affected infants are ill with symptoms of:
•Mineralocoroticoid deficiency.
•Glucocorticoid deficiency.
Congenital defects in the enzymes lead to deficient cortisol
secretion and the syndrome of congenital adrenal hyperplasia.
The hyperplasia is due to increased ACTH secretion.
All the precursor molecules are converted into Androgens which
leads to “virilization” of the infant which means more male
characteristics which will be more apparent in the female child.

(detail with the pathophysiological disorders.)

MECHANISM OF ACTION
 Receptor Types & Specificity
Each of the adrenocortical steroid hormones binds with a receptor
specific for it within the cytoplasm of the hormone’s target cells:

•MR- Mineralocorticoid Receptor: binds a mineralocorticoid.

•GR- Glucocorticoid Receptor: binds a glucocorticoid.
•AR- Androgen Receptor: binds dehydroepiandrosterone.

As is true of all steroid hormones, each hormone-receptor complex

moves to the nucleus and binds with a complementary hormone-
response element in DNA, namely the mineralocorticoid response
element, glucocorticoid response element, and androgen
response element. This binding initiates specific gene transcription
leading to synthesis of new proteins that carry out the effects of the
hormone.
Relative Potency of Natural & Synthetic steroids
Aldosterone's mineralocorticoid activity is about 3000 times
greater than that of cortisol, but the plasma concentration of
cortisol is nearly 2000 times that of aldosterone.

STEROID ORIGIN Glucocorticoid Mineralocorticoid

activity activity

CORTISOL Natural 1.0 1.0

CORTICOSTERONE Natural 0.3 15

ALDOSTERONE Natural 0.3 3000

PREDNISONE Synthetic 4 0.8

9α-FLOROCORTISOL Synthetic 10 125

DEXAMETHASONE Synthetic 25 0
ALDOSTERONE
ALDOSTERONE
Is a mineralocorticoid so called because of its
effect on the minerals (Na & K) of the body.
ACTIONS OF ALDOSTERONE
 In the target organ, when Aldosterone complexes with
MR, it causes increased transcription of mRNAs. This
increases protein synthesis which alters cell function.
Regulation of Aldosterone Secretion:
 POINT TO REMEMBER:

ACTH from the Anterior pituitary is

necessary for Aldosterone secretion but
has little effect in controlling the rate of
secretion!
 DOES ANY OTHER ADRENOCORTICAL
HORMONE HAVE MINERALOCORTICOID
ACTIVITY?
IF SO, THEN WHY DO THEY NOT EXERT
THEIR EFFECT THROUGH THE MR
(MINERALOCORTICOID RECEPTOR)?
WHAT WILL HAPPEN IF THERE ARE NO
MINERALOCORTICOIDS BEING
PRODUCED IN THE BODY?
 Total loss of adrenocortical secretion usually causes death
within 3 days to 2 weeks unless the person receives extensive
salt therapy or injections of mineralocorticoids.

Without mineralocorticoids:
•Potassium ion concentration of the extracellular fluid rises
markedly.
•Sodium and chloride are rapidly lost from the body.
•Total extracellular fluid volume and blood volume become
greatly reduced.
•The person soon develops diminished cardiac output, which
progresses to a shock like state, followed by death.

This entire sequence can be prevented by the administration

of aldosterone or some other mineralocorticoid. Therefore, the
mineralocorticoids are said to be the acute "lifesaving"
portion of the adrenocortical hormones.
WHAT HAPPENS IF THERE IS EXCESS
ALDOSTERONE SECRETION?
What happens if Excess Aldosterone
secretion?
 Aldosterone
Escape
Excess Aldosterone secretion
↓
Na & water retention
↓
Increased blood volume
↓
Pressure Natriuresis &
Pressure Diuresis
↓
Salt & water excretion returns
to normal
↓
This is called Aldosterone
Escape
 Question:
• What is Pressure Natriuresis & Pressure
Diuresis?

• A rise in arterial blood pressure causes

increased excretion of both salt (Pressure
Natriuresis) and water (Pressure Diuresis).
This is due to the secretion of ANP from
the atrial muscles of the heart.
CORTISOL
• Cortisol is a Glucocorticoid so called
because of its effect on glucose levels in the
plasm.
• It is also a derivative of cholesterol.
• About 99% cortisol binds to the plasma
proteins esp. a globulin called Cortisol
Binding Globulin (CBG) or Transcortin.
• Because most of the cortisol is in bound form,
thus, it has a relatively long half-life of 60-90
minutes.
BIOSYNTHESIS of CORTISOL
Cholesterol
↓cholesterol desmolase
Pregnenolone
↓17-α- hydroxylase
17-hydroxypregnenolone
↓3-β-hydroxydsteroid
dehydrogenase
Progesterone →17-hydroxyprogesterone
↓21-β-hydroxylase
11- deoxycortisol
↓11-β-hydroxylase
cortisol
ACTIONS OF CORTISOL
EFFECT ON METABOLISM
CHO METABOLISM
PROTEIN METABOLISM
FAT METABOLISM
FAT METABOLISM
EFFECT ON STRESS &
INFLAMMATION
ACTIONS ON STRESS
The Devastating effects of Inflammation
 How does Cortisol help in resolution of healing?

- Blocks early stages of inflammation preventing it from

starting
- If inflammation already started then it causes its rapid
resolution & hastens healing.
- Blocks the inflammatory response to allergic reactions.
1. Cortisol stabilizes the lysosomal membranes as a primary
effect.
2. Cortisol decreases the permeability of the capillaries as a
secondary effect.
3. Cortisol decreases both migration of White blood cells &
phagocytosis of the damaged cells in the inflamed area.
4. Cortisol suppresses the immune system, esp. decreasing
the lymphocyte reproduction.
5. Cortisol reduces fever as it decreases the release of
interleukin-2.
 Immunosuppressive Effects:
Role in Autoimmune diseases
• Certain diseases respond well to cortisol given as
“steroids”:
- Rheumatoid arthritis
- Rheumatic fever
- Acute Glomerulonephritis
All these diseases are characterized by severe local
inflammation and the harmful effects are caused by
the inflammation itself and not by the disease.
When cortisol is given, then the inflammation subsides
within 24 hours. This prevention of the damaging
effects of the inflammation alone can be a life saving
measure.
It is also given in organ transplant to reduce chances of
rejection.
 Effect of Cortisol on:
WATER & MINERALS ON BONE
• Important role in • It stimulates the bone
maintenance of water resorption (osteoclastic
balance.
activity) and prevents
• Accelerating excretion of
water. bone formation
• Adrenal insufficiency (osteoblastic acitivity).
causes water retention & • So, in hypersecretion of
water intoxication after Cortisol, Osteoporosis
intake of large quantities of
water.
occurs.
• Increases the secretion of
Na & excretion of K.
Effect on Blood Cells & Immunity
REGULATION OF CORTISOL
SECRETION
 ACTH
• Major control is brought about by ACTH
(Adrenocorticotropic hormone) also called Corticotropin
or Adrenocorticotropin.
- Large peptide: 39 aa
- secreted by the cells of the anterior pituitary gland.
- ACTH secretion is regulated by hypothalamus
through the corticotropin-releasing hormone (CRH).
ACTH has the following actions:
1. Maintenance of structural integrity & vascularization of
zona fasiculata & reticularis.
2. Conversion of cholesterol into pregnenolone.
3. Release of glucocorticoids
 ACTH & POMC
Anterior pituitary secretes a large protein as a
Preprohormone called as POMC or
Proopiomelanocortin, which when cleaved causes the
formation of:
• ACTH
• MSH (melanocyte stimulating hormone) which causes
darkening of the skin by stimulating formation of
melanin & dispersing it to the epidermis
• Beta Lipoprotein
• Beta endorphin & few others

ACTH also has 1/30 as much activity of MSH & so its

hypersecretion also causes Hyperpigmentation of the
skin.
Regulation of Cortisol Secretion
Hypothalamus (paraventricular cells)
↓
CRH
↓
Hypophsyial- Hypothalamic portal system
↓
Anterior Pituitary
↓
ACTH
↓
Adrenocortical cells of the adrenal gland
↓
Increased cAMP
↓
Activates the intracellular enzymes esp. Protein kinase A
↓
Conversion of cholesterol to pregnenolone (rate limiting step for all adrenocortical
hormone syn.)
The Diurnal Rhythm for Cortisol
 Question
Scenario 1
• Make a scenario of an • Make a scenario of an
MCQ. Outline the signs
and symptoms that you
would expect in a patient
with hyposecretion of
adrenocortical hormones.
Give 4 options for the
MCQ question.
Scenario 2
MCQ. Outline the signs
and symptoms that you
would expect in a patient
with hypersecretion of
adrenocortical hormones.
Give 4 options for the
MCQ question.