Structure and function of the adrenal gland

Question 1

Describe the location of the adrenal glands

Answer 1

• In the retroperitoneal space next to the kidneys

- Cranial aspect of the kidneys

Question 2

What do the different regions of the adrenal cortex secrete?

Answer 2

• Medulla= catecholamines
• ZG= mineralocortcoids (aldosterone)
• ZF= glucocorticoids (cortisol)
• ZR= androgens (testosterone)

Question 3

Describe the synthesis of steroid hormones

Answer 3

• All cholesterol derived
• Cholesterol is converted into pregnenolone by P450 side chain cleavage enzyme
• Pregnenolone then converted into different hormones dependant on zone of the adrenal gland

Question 4

Describe how cholesterol is converted into pregnenolone

Answer 4

The cholesterol is converted by P450 size chain cleavage enzyme
-This is a rate limiting step and is activated by ACTH

Question 5

What is the average size for a dog’s adrenal glands?

Answer 5

2.5 x 1 x 0.5

Question 6

How is ACTH synthesised?

Answer 6

• From pro-opiomelanocortin (POMC)
• POMC undergoes series of post translation modifications before its proteolytically cleaves to yield various polypeptides with varying physiological actions

Question 7

What are the names of the 2 hormones that cleave POMC?

Answer 7

• Prohormone convertase 1 cleaves POMC

- Prohormone convertase 2 cleaves MSH and Clip

Question 8

Describe the physiology of glucocorticoids

Answer 8

• Transported in blood bound to plasma proteins
• Bind to specific cell membrane receptors
• The receptor-steroid complex is transported to the nucleus
• Results in altered gene expression.

Question 9

Describe the actions of glucocorticoids

Answer 9

• Fat= mobilises fat from peripheral tissue
• Liver= Gluconeogenesis
• Kidney= increases GFR and blocks ADH
• Skin= follicular atrophy, sebaceous gland atrophy, degrades collagen in the skin
• Bone= reduces calcium concentration
• Immune system= releases neutrophils

Question 10

Describe mineralocorticoids

Answer 10

• E.g. aldosterone

- Class of hormones characterised by effects on salt and water

Question 11

What do androgens do?

Answer 11

Stimulate/ control development/ maintenance of male characteristics by binding to androgen receptors
-PRECURSORS FOR ALL OESTROGENS

Question 12

What is the difference between cushings in dogs and in horses?

Answer 12

• In horses it is PPID= a disease of the pars intermedialis

- In dogs it can be either adrenal or the anterior pituitary.

Question 13

Explain the difference between ADH and PDH

Answer 13

• ADH= less common, It is independent of pituitary control, low ACTH
• PDH= most common, adenoma is functional, excess ACTH is produced -bilateral adrenal enlargement

Question 14

Compare the signalment between ADH and PDH

Answer 14

• ADH more common in older dogs, whereas PDH mainly in middle aged dogs
• Predisposed to PDH= poodles, dachsunds, small terriers
• Predisposed to ADH= larger dog breeds

Question 15

What are the classical clinical signs of HAC?

Answer 15

• Pot bellied appearance
• Curly long coat
• PUPD (ADH blockage?)
• Polyphagia (direct affect of glucocorticoids)
• Hepatomegaly
• Skin changes ( anagen phase inhibited by steroids)
• Muscle wastage (due to muscle catabolism)

Question 16

What affect would you expect if you injected a healthy dog with ACTH?

Answer 16

-Increased cortisol (in a HAC dog this response is exaggerated)

Question 17

What affect would you expect if you injected a healthy dog with glucocorticoid?

Answer 17

-Decreased cortisol due to neg feedback on ACTH

Question 18

How does Trilostane work in the treatment of HAC?

Answer 18

It inhibits some of the enzymes involved in the production of glucocorticoids and mineralocorticoids in the adrenal cortex