Adrenal Steroids - Synthesis Transport Metabolism Flashcards
Which is the primary endogenous glucocorticoid?
Cortisol or Hydrocortisone (same thing)
Which is a pro-drug when taken orally (inactive) and which is active? Cortisone or Cortisol
Cortisone is a pro-drug
Cortisol is active
Where is cortisol synthesized?
The cells of the zona fasciculata, zona reticularis
What is cholesterol converted to?
Pregnenolone (the last common precursor of the 3 major adrenal products)
Name an intra adrenal intermediate in the synthesis of Aldosterone?
Progesterone
What is the primary androgen of the adrenal system?
Dehydroepiandosterone (DHEA)
What does the orphan drug Aminoglutethamide do?
Blocks the first step in the synthesis of every steroid (estradiol, testosterone, cortisone, etc) by cleaving the side chain from cholesterol
What is Deoxycorticosterone (DOC)?
It has weak minerocorticoid activity. Sometimes they use it instead of Aldosterone
What does Ketoconazole do?
It is an anti fungal that blocks many of the enzymes used to make steroids that use CYP450.
Where are the glucocorticoids secreted and what modulates it?
Secreted by the adrenal gland and rate is modulated by ACTH
Describe the circadian rate of release of glucocorticoids
Highest serum level is at night and falls off during the day. Release of cortisol is usually at night. Peak at 8am. 7-13 pulses throughout the day.
Which plasma protein carries serum glucocorticoids?
Corticosteroid-binding globulin (CBG). It is a saturable carrier
What increases CBG synthesis?
Estrogens
Where is free cortisol metabolized?
The liver where it is either reduced or oxidized
