Corticosteroids

Question 1

• What are the two natural glucocorticoids?

Answer 1

Cortisol & corticosterone

Question 2

• What would animals suffer if glucocorticoids were absent?

Answer 2

Metabolic derangements & an inability to withstand stress

Question 3

• Explain the hypothalamic-pituitary-adrenal (HPA) axis

Answer 3

Corticotropin-releasing hormone (CRH) from the hypothalamus
ACTH secreted from the pars distalis (anterior pituitary gland)
Increase in P-450 side-chain cleavage enzyme activity (rate limiting)
Cortisol secreted by the zona fasciculata (middle) of the adrenal cortex
Negative feedback to the pituitary gland and hypothalamus

Question 4

• What are the species specific surges of cortisol seen in horses, pigs & dogs?

Answer 4

Horses – one morning surge, pigs – morning and late afternoon surges, dogs – no surges

Question 5

• What is the prohormone of ACTH?

Answer 5

Proopiomelanocortin (POMC)

Question 6

• What is ACTH?

Answer 6

Water-soluble hormone which binds to membrane receptors, G protein activates adenyl cyclase, formation of cAMP, activates protein kinase A, phosphorylates cholesterol ester hydrolase, increases enzyme activity in the zona fasciculata

Question 7

• How is cortisol transported?

Answer 7

Secreted as a free hormone, binds to cortisol-binding globulin – 70%, or albumin – 15%

Question 8

• What are the general actions of corticosteroids?

Answer 8

Stress hormone – triggers epinephrine release
Carbohydrates – immediate glycogenolysis, long-term gluconeogenesis
Glucose utilization – inhibits normal physiology of insulin
Lipids – stimulates enzymatic hydrolysis of triglyceride (hormone-sensitive lipase)
Proteins – increases gluconeogenesis
Growth inhibition – inhibition of DNA synthesis, muscle atrophy
Anti-inflammatory – counterbalance to inflammatory response

Question 9

• What are the anti-inflammatory effects of cortisol?

Answer 9

Stabilizes lysosomal membranes, decreases the permeability of capillaries, decreases migration of leukocytes, suppresses lymphocyte production, reduces interleukin-1 release

Question 10

• What is the classic mineralocorticoid?

Answer 10

Aldosterone

Question 11

• Why can cortisol be described as dual action?

Answer 11

Also possesses some mineralocorticoid activity, as well as glucocorticoid

Question 12

• What two factors activate aldosterone?

Answer 12

High potassium levels & RASS responding to reduced blood volume

Question 13

• Where is the main action of aldosterone?

Answer 13

Principal cells of the collecting ducts

Question 14

• What are the effects of aldosterone?

Answer 14

Increase synthesis of channel proteins in the luminal membrane and sodium-potassium ATPase pump on basolateral membrane