Glucocorticoids Flashcards
Describe the difference between glucocorticoids and mineralocorticoids.
Glucocorticoids are “stress hormones”. Their main effects are increasing blood sugars and immune suppression (utility in asthma prophylaxis). Mineralocorticoids are involved in blood pressure regulation and Na/K levels.
From which gland are glucocorticoids and mineralocorticoids secreted?
adrenal cortex
Contrast the modes of action of two stress hormones: epinephrine and cortisol.
Epinephrine is involved in a more immediate response. It signals glycogenolysis in the liver. Its receptor is a GPCR on the cell surface.
Cortisol binds to an intracellular receptor and alters gene expression. Thus, it produces a prolonged biological response. It induces gluconeogenic enzymes.
Name the effect of glucocorticoids on the following body parts: liver, adipose tissue, immune system, muscle.
liver: induces gluconeogenesis and increases glycogen storage
adipose tissue: fatty acid breakdown, decrease sensitivity to insulin
immune system: suppression (decr. cytokine and eicosanoid production)
muscle: promotes protein breakdown, decreases protein synthesis and insulin sensitivity
Glucocorticoids up regulate gene expression of enzymes for ___________ and ______________.
gluconeogenesis, anti-inflammatory proteins
One example of an anti-inflammatory protein induced by glucocorticoids is lipocortin-1. How does it reduce inflammation?
suppression of phospholipase A2, critical in the synthesis of eicosanoids
Explain how glucocorticoids suppress immune function by altering the NFκB pathway?
Normally, NFκB is induced by immune cell activation. If glucocorticoid receptors have been activated, however, they block binding of activated NFκB to DNA.
Two major risks of glucocorticoid therapy include __________ with excess glucocorticoids, and __________ upon too rapid of a withdrawal.
Cushing’s syndrome, Addisonian crisis
Fludrocortisone contains which structural modification? What effect does this have on GC and MC activity?
9α-F, enhances GC but greatly incr. MC activity –> used in MC replacement therapy
What structural modification is made to prednisone and prednisolone? What is the consequence of this?
There is an extra double bond between C1 and C2. This enhanced GC activity and reduced MC activity.
Which synthetic glucocorticoid contains a 6α-methyl group and has similar activity to that of prednisolone?
methylprednisolone
Which synthetic glucocorticoid has similar activity to prednisolone, but an additional 9α-F and a 16α-OH? (also has increased hydrophilicity)
Triamcinolone
Which two enantiomers contain a 16α-methyl group that adds lipophilicity and creates the most potent GC activity with the least MC activity?
dexamethasone and betamethasone
What are some adverse effects associated with corticoid therapy?
(1) crossover MC activity
(2) steroid myopathy (muscle wasting)
(3) reduced long bone growth in children
(4) osteoporosis
(5) Cushing’s-like effects
(6) impaired glucose tolerance
(7) immune suppression
(8) incr. ulcer risk
What is an Addisonian crisis?
It occurs with abrupt withdrawal of corticoid therapy. Prolonged negative feedback of the hypothalamus and pituitary occur with corticoid therapy. After abrupt withdrawal,, there is delayed recovery by these two areas in the brain (decr. ACTH release). The body cannot deal with stress now. Should be treated as a medical emergency and can be fatal.
