T1 L6 - Adrenal Cortex - Hormones, Physiology

Question 1

What are the adrenal glands divided into?

Answer 1

They are divided into the inner adrenal medulla (10%) and the outer adrenal cortex (90%)

Question 2

What are hormones synthesised from the adrenal cortex derived from?

Answer 2

Cholesterol obtained from the diet or synthesised within the gland itself.

Question 3

What are the 3 layers of the adrenal cortex?

Answer 3

• Zona glomerulosa
• Zona fasisculata
• Zona reticularis

Question 4

What are the classifications of steroid hormones produced by the adrenal glands?

Answer 4

• Glucocorticoids (eg cortisol)

- Mineralocorticoids (eg aldosterone)

Question 5

How is glucocorticoid secretion controlled?

Answer 5

The hypothalamus secretes CRH
CRH stimulates the anterior pituitary gland to release ACTH
ACTH stimulates the adrenal cortex to release cortisol
Cortisol inhibits CRH release in the hypothalamus

Question 6

Describe the pattern of ACTH secretion.

Answer 6

ACTH secretion is pulsatile.
It peaks in the early morning, at the time of waking
It nadirs in the middle of the night.

Cortisol secretion shows the same pattern but the peak and nadir occur approximately 2hrs later than those of ACTH.

The pattern is related to sleep - wake patterns. It is disrupted by shift work and long-haul travel.

Question 7

How is cortisol transported in the blood?

Answer 7

Only 10% of cortisol is free in the blood.
The remainder is bound to the plasma proteins:
-Corticosteroid binding globulin (CBG or transcortin) (75%)
-Albumin (15%)

The same proteins also transport the other glucocorticoids and progesterone.

Question 8

What is associated with an increase in CBG?

Answer 8

Pregnancy which leads to a compensatory increase in circulating plasma cortisol concentrations.

The amount of free cortisol remains the stable.

Question 9

Where does metabolism of adrenal steroids occur? And how are they metabolised?

Answer 9

Adrenal steroids are mainly metabolised in the liver.

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

Question 10

How do glucocorticoids produce their effect?

Answer 10

They produce their effect by acting on intracellular receptors and altering gene expression.

Question 11

What are the actions of cortisol at normal physiological concentrations?

Answer 11

It’s important actions are on carbohydrate metabolism. Cortisol is opposite to insulin:

• Stimulate glycogenolysis
• Antagonises effects of insulin on cellular glucose uptake
• Stimulates hepatic gluconeogenesis

It also:
-Stimulates lipolysis and mobilization of fatty acids by partially potentiating the effects of growth hormone and catecholamine

Question 12

What effects does cortisol have at excessive concentrations?

Answer 12

In excessive concentrations cortisol causes fat synthesis and deposition in novel anatomical sites, most notably the face, the trunk and intrascapular region of the shoulders.

It also enhances the vasoconstrictor response to catecholamine which may result in increased blood pressure.

Question 13

What other effects can glucocorticoids produce?

Answer 13

They can produce psychological effects with possible feelings of elation or sedation.

Question 14

When is there a rapid secretion of ACTH and corticosteroids?

Answer 14

At times of psychological and physiological stress such as trauma, infection or hypoglycaemia.

At these concentrations the additional effects of these hormones become apparent.

Question 15

How do glucocorticoids affect the body’s defence system?

Answer 15

• suppressed lymphoid tissue, reduced antibody production and inhibition of cellular immune system
• They stabilise the leucocyte membrane and reduce the release of proteolytic enzymes.
• The inhibit phospholipase A2, and reduce the synthesis of inflammatory mediators.

Question 16

Why are glucocorticoids beneficial even though they appear to potentiate the adverse effect of an injury and retard tissue repair?

Answer 16

• The adrenocortical stress response decreases the inflammatory response.
• It removes pain and decreases the immobilisation caused by the oedema.
• Steroid induced sedation also causes a lack of awareness of the severity pf the situation.
• The overall effect is that the individual is able to perform despite the presence of an injury or infection.

Question 17

How does cortisol affect the liver in comparison to the periphery?

Answer 17

In the liver cortisol enhances amino acid uptake enhancing gluconeogenesis.
In the periphery it prevents amino acid uptake and protein synthesis, resulting in a net loss of skeletal protein.

Question 18

What other receptors can glucocorticoids stimulate?

Answer 18

They can also stimulate aldosterone receptors although aldosterone sensitive tissues possess an enzyme, 11B(eta)-hydroxysteroid dehydrogenase1, which converts cortisol to inactive cortisone.

Mineralocorticoid actions of glucocorticoids are only apparent at high concentrations.

Question 19

Name 2 physiologically important mineralocorticoids?

Answer 19

• aldosterone

- 11-deoxycorticosterone

Question 20

What is the major controlling factor in the secretion of aldosterone?

Answer 20

The renin-angiotensin system

Question 21

What does ACTH stimulate the conversion of in the adrenal cortex?

Answer 21

It stimulates the conversion of cholesterol to pregnenolone.

Question 22

What is the secretion of aldosterone stimulated by?

Answer 22

• trauma
• anxiety
• hyperkalaemia
• hyponatraemia

Question 23

What is aldosterone inhibited by?

Answer 23

Atrial natriuretic peptide (ANP)

Question 24

Within the circulation how much of aldosterone is protein bound?

Answer 24

50%

Question 25

What is the mechanism of aldosterone?

Answer 25

It has specific intracellular receptors which cause exppression of ion channels that transport sodium and potassium ions across the cell membrane.

Question 26

Where does aldosterone stimulate the reabsorption of sodium ions?

Answer 26

In the kidney: Mainly the distal tubule Lesser effects in the collecting duct, proximal tubule and ascending loop of henle. Also in the COLON, SWEAT and SALIVARY GLANDS.

Question 27

What are the pharmacological uses of glucocorticoids?

Answer 27

- They are used in replacement therapy - For their immunosuppressive o anti-inflammatory effects such as in conditons like arthritis, asthma or allergies - Can also be used in proliferative conditions such as leukaemia.

Question 28

What are the pharmacological uses of Mineralocorticoids?

Answer 28

They are used only for replacement therapy. Aldosterone has a short plasma half-life rendering it unsuitable for mineralocorticoid replacement therapy. Drug of choice is fludrocortisol.

Question 29

What are some adverse effects associated with the use of glucocorticoids?

Answer 29

- Steroid usage may suppress wound healing and may exacerbate infection due to their immunosuppresant effects. - In children long term use may cause growth inhibition and it can cause osteoperosis in adults - The development of diabetes mellitus and other symptoms of cushing's syndrome also often accompany steroid therapy.

Question 30

What is the most important adverse effect of glucocorticoid use?

Answer 30

It suppresses the hypothalamic-pituitary axis. Chronic administration of exogenous glucocorticoids can result in suppression of ACTH secretion leading to atrophy of the adrenal cortex.

Question 31

What happens when steroid hormone is stopped abruptly?

Answer 31

The adrenal cortex is unable to secrete endogenous hormones and the patient suffers from addisonian crisis, which may be fatal. Overcome by the gradual reduction of the dose of exogenous steroid.

Question 32

What's a consequence of suppression of the anterior pituitary?

Answer 32

It may disturb the secretion of sex hormone resulting in symptoms such as menstrual disturbances.