Although progesterone reaches up to 100 times higher plasma levels in late pregnancy than aldosterone, the in vivo mineralocorticoid antagonistic effect of progesterone seems to be relatively weak. One explanation for this phenomenon could be local metabolism of progesterone in the human kidney, similar to the inactivation of cortisol to cortisone by HSD11B2. Using human kidney cortex microsomes, Quinkler et al. (1999) tested the inhibitory potency of progesterone and its metabolites on HSD11B2. The most potent inhibitor was progesterone itself. The authors concluded that inhibition of HSD11B2 leads to an increase of intracellular cortisol in such a way that the local equilibrium between the mineralocorticoid agonist cortisol and the antagonist progesterone is shifted to the agonist side, suggesting a role in preeclampsia.
Congenital adrenal hyperplasia is a metabolic disorder related to enzymatic defects in the biosynthesis of cortical steroids. Typically the defects are inherited in an autosomal recessive manner, and within a particular family all inherit the same enzyme deficiency (1).