Intracellular regeneration of active steroids cortisol from cortisone (in humans) and corticosterone from 11-dehydrocorticosterone
(in rodents) is achieved through 11[beta]-HSD type 1 (11[beta]-HSD1), a lower-affinity NADP(H)-dependent enzyme that acts as oxoreductase in tissues with high sensitivity to glucocorticoids .
(13) Kendall isolated 6 active adrenocortical hormones from the adrenal gland and named them in the order in which they were isolated, i.e., Compound A through F (Compound A is 11-dehydrocorticosterone
, Compound B is corticosterone or Reichstein's substance H, Compound C is 5[alpha]-pregnane-3[alpha], 11[beta], 17[alpha], 21-tetrol-20-one or Reichstein's substance C, Compound D is 5[alpha]-pregnane-3[beta], 11[beta], 17[alpha], 20[beta], 21-pentol or Reichstein's substance A, Compound E is cortisone or Reichstein's substance F, and Compound F is cortisol or Reichstein's substance M).
Since glucocorticoids (cortisol in humans and corticosterone in rodents) and mineralocorticoids (aldosterone) both bind to MR with relatively high affinity, the MR specificity of aldosterone in epithelial cells in humans is due to the intracellular inactivation of cortisol to cortisone (and corticosterone to 11-dehydrocorticosterone
in rodents) by the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11HSD2) (Figure 1).
Endogenous glucocorticoids exist either as active 11-hydroxy steroids (cortisol and corticosterone) that bind GR or as inactive 11-oxo derivatives (cortisone and 11-dehydrocorticosterone
), which do not bind to GR (Ergang et al.
Compound A (11-dehydrocorticosterone
) and Compound E (cortisone) were chosen for the initial studies owing to their structural simplicity.
In the placenta the fetus is protected from the high maternal glucocorticoid concentration through the activity of 11[beta]-hydroxysteroid dehydrogenase type 2 (11[beta]-HSD2), which converts active 11[beta]-hydroxyglucocorticoids (cortisol in human, corticosterone in rodents) into inactive 11-ketoglucocorticoids (cortisone in human, 11-dehydrocorticosterone
in rodents) (reviewed in Stewart and Krozowski 1999).
The enzyme 11[beta]-hydroxysteroid dehydrogenase type 2 (11[beta]-HSD2) converts corticosterone to 11-dehydrocorticosterone
in the distal convoluted tubules and cortical collecting ducts in rats, and cortisol to cortisone in humans.