LOCAL
DEHYDROGENATION OF THE C11 HYDROXYL GROUP ON CORTISOL
PROTECTS MINERALOCORTICOID RECEPTORS (MR)
FROM
INAPPROPRIATE ACTIVATION
ALDOSTERONE:MR
Kd~1nM CORTISOL
or CORTISONE : MR Kd~1nM
CORTISOL or CORTISONE : GR
Kd~10nM
IN
SPITE OF THE HIGH AFFINITY OF CORTISOL / CORTISONE FOR THE MR IN VITRO, GLUCOCORTICOIDS DO NOT BIND TO MR IN TARGET TISSUES. THIS IS DUE
TO THE �PRE-RECEPTOR INACTIVATION� OF CORTISOL BY 11�-HSD2
CORTISOL
GR
11�-HSD1
CORTISOL
nucleus
CORTISOL
11�-HSD2
CORTISONE
KIDNEY,COLON
SALIVARY
GLAND,
HEART
OXIDATION
OF
C11 HYDROXYL
nucleus
NO RESPONSE
MR
RESPONSE