Adrenal cortex- hormones, physiology

Question 1

Adrenal glands

Answer 1

Lie on top of the kidneys

Divided into the inner adrenal medulla and the outer adrenal cortex

Medulla is concerned with stress response

Cortex is concerned with stress, sodium and glucose homeostasis

Functional adrenal cortex is essential for life

Question 2

Adrenal cortex synthesises

Answer 2

Many different hormones of a similar chemical structure (steroid hormones)

Derived from cholesterol

Question 3

Three distinct layers of the adrenal cortex

Answer 3

Outer zona glomerulosa

Middle zona fasciculata

Innermost zona reticularis

Question 4

Major secretions of the adrenal cortex

Answer 4

Glucocorticoids (e.g. cortisol)

Mineralocorticoids (e.g. aldosterone)

Question 5

Zona glomerulosa synthesis

Answer 5

18-hydroxylase enzyme

Hence aldosterone synthesis

Question 6

Zona fasciculata and zona reticularis synthesis

Answer 6

17a-hydroxylase

Hence 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and the hormones derived from them

Cortisol is synthesised from ZF

Androgens are synthesised from ZR

Question 7

Secretions from the adrenal cortex under normal circumstances

Answer 7

Small quantities of male sex hormones such as dehydroepiandrosterone, androstenedione and testosterone

Female sex oestrogens e.g. oestradiol

Question 8

Control of glucocorticoid secretion

Answer 8

Hypothalamus releases CRH

Acts on anterior pituitary to release ACTH

Acts on adrenal cortex to release cortisol

Feeds back to the hypothalamus

Question 9

Pulsatile secretion of ACTH

Answer 9

Peak in the early morning at the time of waking

Nadir in the middle of the night

Increased secretion at time of prolonged stress

Cortisol shows the same pattern but 2 hours later

Question 10

Transport of glucocorticoids

Answer 10

Only 10% of cortisol within the blood is in a free, active form

Remained bound to plasma proteins

• corticosteroid binding globulin (75%)
• albumin (15%)

The same proteins also transport other glucocorticoids and progesterone

Question 11

Metabolism of adrenal steroids

Answer 11

Occurs mainly in the liver

They are glucuronidated to form water soluble forms which are excreted in the urine

Question 12

Action of glucocorticoids

Answer 12

Action on intracellular receptors and alterations in gene expression

Inevitably results in a delay in hours or days

In some cases the effects of cortisol are rapid e.g. feedback inhibition of ACTH secretion

Question 13

Most important actions of cortisol

Answer 13

To do with carbohydrate metabolism

Opposite to insuline

• antagonises the effects of insulin on cellular uptake of glucose
• stimulates glyocenolysis
• stimulates hepatic gluoneogenesis

Stimulates lipolysis and mobilisation of fatty acids

Question 14

Excessive concentrations of cortisol causes

Answer 14

Fat synthesis and deposition in novel anatomical sites

• face
• trunk
• intrascapular region of the shoulders

Question 15

Cortisol in the liver

Answer 15

Simulates amino acid uptake leading to enhanced gluconeogenesis

Question 16

Cortisol in the periphery

Answer 16

It inhibits amino acid uptake and protein synthesis

Results in a net loss of skeletal protein

Question 17

Excess cortical response to catecholamines

Answer 17

Enhanced vasoconstrictor response

Results in increased blood pressure

Question 18

Glucocorticoid psychological effects

Answer 18

Possible feelings of elation of sedation

Question 19

Times of psychological and physiological stress

Answer 19

e.g.g trauma, infection, hypoglycaemia

Rapid secretion of ACTH and corticosteroids

At these raised concentrations, additional effects of hormones become apparent

Question 20

Glucocorticoids effects of the body’s defence system

Answer 20

Suppress lymphoid tissue, reduce the antibody production and inhibit cellular immune system

Stabilise leucocyte membranes and reduce the release of proteolytic enzymes

Inhibit phospholipase A2 and reduce the synthesis of inflammatory mediators

Question 21

Most important role of glucocorticoids

Answer 21

Response to stress

In the absence of corticosteroids even mid stress can be fatal

Question 22

Glucocorticoids and prolonged stress

Answer 22

Maintain the enhanced supply of glucose which may be required for the prolonged response to the stress

Suppress the inflammatory response

Question 23

At times of injury

Answer 23

Pain alerts the sufferer to the damage

Oedema dilutes any toxic substances that may be present and immobilises and stabilises joints

Infiltration by leucocytes destroys any invading cells whilst antibodies inactivate the foreign proteins

Tissue repair is enhanced by prostaglandins

Question 24

Adrenocortical stress response and injury

Answer 24

Decreases the inflammatory response

Removes the pain and decreases the immobilisation induced by oedema

Steroid induced sedation also causes lack of awareness of severity of the situation

Overall effect leads individual to perform despite the presence of injury or infection

Question 25

Control of mineralocorticoid secretion

Answer 25

Aldosterone and 11-deoxycorticosterone are the physiologically important mineralocortcioids

Secretion of aldosterone uninfluenced by ACTH, major controlling factor in the RAAS

Secretion of aldosterone stimulated by trauma, anxiety, hyperkalaemia, hyponatraemia

Aldosterone inhibited by atrial natriuretic peptide

Question 26

Actions of mineralocorticoids

Answer 26

Aldosterone has specific intracellular receptors, cause expression of ion channels that transport sodium and potassium ions

Aldosterone stimualtes reabsorption of Na+ in distal tubule

Na+ reabsorption in exchange for K+ or H+

Question 27

Pharmacological uses of adrenocorticosteroids

Answer 27

Glucocorticoids used in replacement therapy for immunosuppressive or anti-inflammatory effects in conditions

• arthritis
• asthma
• allergies

Used in treatment of some proliferative conditions such as leukaemia

Question 28

Adverse effects associated with glucocorticoids

Answer 28

Steroid usage may suppress wound healing and may exacerbate infections due to their immunosuppressant effects

Long term use in children may cause inhibition of growth, and in adults may result in osteoporosis

The development of diabetes mellitus and other symptoms of Cushing’s also often accompanies steroid therapy

Question 29

Most important adverse effect of glucocorticoids

Answer 29

Suppression of the hypothalamic- pituitary axis

Chronic administration of exogenous glucocorticoids results in the suppression of ACTH secretion

Leads to atrophy of the adrenal cortex