Page 1 Glucocorticoids 1 2/4/2026
11β-HSD (Type I) reactivates cortisone to cortisol in liver
11β-HSD (Type II) catalyzes oxidation of cortisol to cortisone in epithelial (kidney) cells
Cortisone does not bind to MR or GR
11β-HSD protects renal tubule cells from circulating cortisol, which is much
more abundant that aldosterone
Type II enzyme is found only in aldosterone-sensitive cells
Aldosterone is not oxidized by 11β-HSD due to C-18 ketone
11β-Hydroxysteroid Dehydrogenase- A Key Enzyme The mineralocorticoid receptor is the ancestral protein to the glucocorticoid
receptor
Binds aldosterone and cortisol with about equal affinity
The GR evolved from MR by gaining selectivity for cortisol
Addition of a double bond at the 1-2 position of enhances glucocorticoid potency 4-5-fold without affecting
glucocorticoid mineralocorticoid potency
Also slows metabolism
Prednisone (Deltasone), prednisolone
Glucocorticoids 1 1 Glucocorticoids 1
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Addition of a fluorine to C9 increases both glucocorticoid (10-fold) and mineralocorticoid activity (125-
fold)
Used in aldosterone replacement therapy
Fludrocortisone (Florinef)
Addition of a hydroxyl or methyl group at C16 enhances potency by 2.5-fold
Eliminates mineralocorticoid effect
Addition of a methyl group to C6 further enhances glucocorticoid potency 1-2-fold and reduces
mineralocorticoid potency by half
Methylprednisone/methylprednisolone (Medrol)
Aldosterone Aldosterone is principal mineralocorticoid
Regulates sodium balance in body
Promotes K+ loss in urine in exchange for Na+
CYP11B2 oxidizes C18 methyl group to ketone: Found only in zona
glomerulosa of adrenal cortex (outermost zone)
Deficiency very rare: Leads to salt wasting, but no effect on cortisol or sex
steroids
Glucocorticoids 1 2 Glucocorticoids 1
11β-HSD (Type I) reactivates cortisone to cortisol in liver
11β-HSD (Type II) catalyzes oxidation of cortisol to cortisone in epithelial (kidney) cells
Cortisone does not bind to MR or GR
11β-HSD protects renal tubule cells from circulating cortisol, which is much
more abundant that aldosterone
Type II enzyme is found only in aldosterone-sensitive cells
Aldosterone is not oxidized by 11β-HSD due to C-18 ketone
11β-Hydroxysteroid Dehydrogenase- A Key Enzyme The mineralocorticoid receptor is the ancestral protein to the glucocorticoid
receptor
Binds aldosterone and cortisol with about equal affinity
The GR evolved from MR by gaining selectivity for cortisol
Addition of a double bond at the 1-2 position of enhances glucocorticoid potency 4-5-fold without affecting
glucocorticoid mineralocorticoid potency
Also slows metabolism
Prednisone (Deltasone), prednisolone
Glucocorticoids 1 1 Glucocorticoids 1
, Page 2 Glucocorticoids 1 2/4/2026
Addition of a fluorine to C9 increases both glucocorticoid (10-fold) and mineralocorticoid activity (125-
fold)
Used in aldosterone replacement therapy
Fludrocortisone (Florinef)
Addition of a hydroxyl or methyl group at C16 enhances potency by 2.5-fold
Eliminates mineralocorticoid effect
Addition of a methyl group to C6 further enhances glucocorticoid potency 1-2-fold and reduces
mineralocorticoid potency by half
Methylprednisone/methylprednisolone (Medrol)
Aldosterone Aldosterone is principal mineralocorticoid
Regulates sodium balance in body
Promotes K+ loss in urine in exchange for Na+
CYP11B2 oxidizes C18 methyl group to ketone: Found only in zona
glomerulosa of adrenal cortex (outermost zone)
Deficiency very rare: Leads to salt wasting, but no effect on cortisol or sex
steroids
Glucocorticoids 1 2 Glucocorticoids 1
