ADRENOCORTICAL

HORMONES

DR ASMA JABEEN

Learning Objectives

By the end of lecture, the students should be able to:

• Describe the functional anatomy of adrenal gland• Describe the functions of mineralocorticoids.• Describe the regulation of mineralocorticoids.• Discuss the functions of glucocorticoids• Describe the effects of abnormal secretion of corticosteroids

The Adrenal Gland

▪15 % of adrenal cortex

▪ Secretes aldosterone

Zona Fasciculata :

▪Widest layer, 75 %

▪ Secretes glucocorticoids ,

cortisol and corticosterone,

androgens and estrogens

Zona glomerulosa

Zona Reticularis:

▪Adrenal androgens , DHEA and

androstenedione

▪ Small amount of estrogens

and some glucocorticoids

Cortical hormones

➢ Mineralocorticoids

➢ Glucocorticoids

➢ Androgens

Medullary hormones

➢ Epinephrine

➢ Nor epinephrine

Adrenal Hormones

Synthesis of Adrenal steroids

▪ 80% of cholesterol is provided by low

density lipoproteins (LDL) in the plasma

▪ LDL receptors in coated pits on adrenocortical

cell membrane - internalization- release of

cholesterol

▪ ACTH increases the no. of LDH receptors &

enzymes

General features

▪ These are steroids derived from

cholesterol

▪ 90 to 95% 0f cortisol bound to plasma

protein transcortin → long half life of 60 to

90 min

▪ 60% of aldosterone bound to plasma

proteins → half life of 20 min

▪ Adrenocortical hormones are metabolized

in the liver

Mineralocorticoids - Aldosterone

Mechanism of action of aldosterone

Functions of the Mineralocorticoids-

Aldosterone

Increased tubular reabsorption of sodium

and secretion of potassium

▪ Main effect is on PRINCIPAL CELLS of

renal tubules causing sodium

conservation in ECF ,increasing

potassium excretion in the urine

Effects of excess aldosterone

➢ Increased extracellular fluid volume and

arterial pressure

➢ Hypokalemia and muscle weakness

➢ Increased tubular hydrogen ion secretion

leading to mild alkalosis

1. Increased extracellular fluid volume

and arterial pressure

▪ Aldosterone decreases the rate of sodium

excretion by kidneys but conc. of sodium

rises only a few meq.

▪ Aldosterone mediated increase of ECF for

more than 2 days → increased arterial

pressure

▪ The rise in arterial pressure increases

kidney excretion of both salt and water

despite excess aldosterone by pressure

natriuresis and pressure diuresis.

▪ These mechanisms return the renal

output of salt and water to normal despite

excess aldosterone. Mechanism is

called aldosterone escape.

2. Hypokalemia and muscle weakness

Excess aldosterone

Loss of potassium

in urine

Transport of K

from ECF to ICF

Alteration in electrical excitability of

nerve and muscle → muscle weakness

Deficient aldosterone

Potassium in ECF above normal

Cardiac toxicity

Heart failure

3. Tubular secretion of hydrogen and

mild alkalosis

➢ Aldosterone causes secretion of

hydrogen ions in exchange for sodium

in intercalated cells of renal cortical

collecting tubules

➢ Decreased hydrogen ions in ECF →

mild alkalosis

▪ Aldosterone increases the reabsorption

of sodium and secretion of potassium by

the ducts of salivary glands and sweat

glands.

▪ It enhances the sodium reabsorption by

the intestines preventing loss of sodium

in stools.

▪ Total loss of Adrenocortical secretion

causes death within 3 days to 2 weeks

▪ Aldosterone is called the Life saving

portion of adrenocortical hormones. Its

administration can reverse the condition

Regulation of Aldosterone Secretion

The regulation is independent of the

regulation of cortisol and androgen .

❑ Increased potassium ion conc. in ECF

❑ Increased Angiotensin II conc, in ECF

❑ Decreased Sodium ion conc. in ECF

❑ ACTH from anterior pituitary

Glucocorticoids- Cortisol

FUNCTIONS OF GLUCOCORTICOIDS

▪ 95% of glucocorticoid activity is by

cortisol ( hydrocortisone)

▪ Metabolic functions → glucose, fats and

carbohydrates

▪ Role of cortisol in stress and inflammation

▪ Permissive action of cortisol

Effects of cortisol on carbohydrate

metabolism

Stimulation of Gluconeogenesis:

Formation of carbohydrates from proteins

and other substances by the liver.

▪ Increase in enzymes required to convert

amino acids into glucose in the liver cells.

( Activation of DNA transcription)

▪ Mobilization of amino acids from

extra hepatic tissues mainly from muscles.

▪ Increased gluconeogenesis causes marked

increase in glycogen storage in the liver cells .

Decreased glucose utilization by the cells:

▪ Moderate decrease in rate of glucose utilization

by most cells of the body .

▪ Decreased translocation of GLUT 4 to the cell

membrane-Insulin resistance in sk.muscles

▪ Reduced expression of Insulin receptor substrate-1

& phosphatidylinositol

▪ Decreased oxidation of NADH to form NAD,

required to allow glycolysis.

▪ Adrenal diabetes & insulin resistance

Effects of Cortisol on Protein metabolism

Reduction in cellular proteins:

▪ Reduction of protein stores in all body

Cells except liver.

▪ ↓ amino acid transport into extra hepatic

cells ( muscle and lymphoid tissue) →

↓ protein synthesis and ↑ protein

catabolism

▪ Increased blood amino acids

Increase of liver and plasma proteins:

▪ Cortisol increases amino acid transport into liver

cells and enhance the liver enzymes required for

protein synthesis- more plasma proteins

▪

Effects of Cortisol on Fat metabolism

Mobilization of fatty acids:

▪ Promotes fatty acid mobilization from adipose

tissue, increased fatty acids in blood and

increased utilization of fatty acids for energy.

▪ α- glycerophosphate derived from glucose

is required for deposition and maintenance

of TGs in the cells.

A peculiar type of obesityin peoplewith excess cortisol

Permissive action of Cortisol:

Small amounts of glucocorticoids must

be present for a number of metabolic

reactions to occur, although they do not

produce the reactions themselves. This

effect is called their permissive action.

e.g for glucagon and catecholamines for

their calorigenic, lipolytic and pressor

responses.

Role of cortisol in Stress

➢ Stress causes immediate and marked ↑

in ACTH followed within minutes by

increased cortisol levels.

➢ Glucocorticoids mobilizes fats and amino

acids from their cellular stores and make

them immediately available for energy.

Role of cortisol in inflammation

▪ Cortisol blocks the early stages of

inflammation even before inflammation

begins.

▪ If inflammation has begun, it causes

rapid resolution of inflammation and

cause rapid healing.

Effect of cortisol on blood cells:

• Excess cortisol causes polycythemia

• Eosinopenia

• Atrophy of lymphoid tissue → ↓ T cells

and antibodies → ↓ immunity for all

foreign invaders of the body

Regulation of Cortisol Secretion

Circadian rhythm of glucocorticoid Secretion

Adrenal Androgens

▪ Moderately active male hormones-

Dehydroepiandrosterone

Contribute in:

• Early development of sex organs in males

• Growth of pubic and axillary hair in females

ADDISON’s DISEASE

(Primary adrenal insufficiency)

It results from the failure of adrenal

cortices to produce adrenocortical hormones.

Causes

▪ Primary atrophy of the adrenal cortices

caused by autoimmunity

▪ Tuberculous destruction

▪ Cancer

Secondary adrenal insufficiency

Secondary to impaired function of pituitary gland

which fails to produce sufficient ACTH.

Mineralocorticoid deficiency::

➢ Hyponatremia, hyperkalemia and

mild acidosis

➢ ↓ plasma volume ,↑ RBC conc.

➢ ↓ cardiac output and shock

Glucocorticoid deficiency:

➢ Inability to maintain normal blood glucose

conc. between meals due to ↓ gluconeogenesis

➢ ↓ mobilization of fats and proteins →

sluggishness of energy mobilization

➢ ↑ susceptibility to infection/ stress

Melanin pigmentation:

➢ Blotches of melanin pigmentation

➢ Negative feedback effect → ↑ ACTH

↑ MSH → Stimulation of melanin

pigmentation by melanocytes.

Addisonian crisis:

An acute need of excessive amount of

glucocorticoids in stress, trauma or disease

and associated severe debility is called

addisonian crisis.

Cushing’s Syndrome

A clinical condition produced by prolonged

increase in plasma glucocorticoids

It was described by Harvey Cushing.

❑ ACTH - Independent CS

❑ ACTH – Dependent CS

It can also occur after prolonged treatment with

Glucocorticoids in chronic inflammatory conditions

Causes of ACTH- independent Cushing’s

Syndrome:

▪ 20 to 25% cases

▪ Glucocorticoid secreting adrenal tumors

▪ Adrenal hyperplasia

▪ Prolonged administration of exogenous

glucocorticoids

Causes of ACTH dependant Cushing’s

Syndrome:

▪ ACTH secreting tumors of anterior

pituitary gland (Cushing’s Disease)

▪ Excessive secretion of CRH from hypothalamus

▪ Ectopic ACTH secretion from some carcinomas

Effects on carbohydrate metabolism:

➢ Increased blood glucose levels

(200mg/dl) after meals

➢ Increased gluconeogenesis

➢ Decreased glucose utilization by the

cells

Effects on protein metabolism:

➢ Decreased proteins -with the exception of liver

and plasma proteins.

➢ Loss of proteins from muscles

➢ Loss of protein synthesis from lymphoid

tissues → suppressed immune system

➢ ↓ protein collagen fibers in subcutaneous

tissue → large purplish striae

➢ Osteoporosis

Redistribution of body fat

▪Buffalo torso or buffalo

hump

▪ Moon face

▪ Lemon on match

sticks

Cushing’s syndrome

Dexamethasone Test:

This test is done to distinguish between

ACTH- dependant and ACTH- independent

Cushing’s syndrome.

Treatment of cushing’s syndrome:▪ Surgery for removal of pituitary tumor

▪ Drugs

▪ Partial or total adrenalectomy

Primary Aldosteronism

(Conn’s Syndrome)

Tumor of zona glomerulosa secreting

large amounts of aldosterone results in

primary aldosteronism or conn’s syndrome

Adrenogenital Syndrome

Excessive production of androgens by an

adrenocortical tumor causing:

• Early masculinizing effects in male child

throughout the body.

• Masculinizing effects in female

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