The mechanism by which the glycyrrhizinates exert their effect on the renin-angiotensin-aldosterone system has been elucidated. 2 , 35 , 36 , 42 Competitive (and reversible) inhibition of the enzyme 11-beta-hydroxysteroid dehydrogenase results in the suppression of cortisol conversion to inactive cortisone. Consequent suppression of plasma renin activity and aldosterone levels is evident. Exchangeable sodium levels increase and cortisol occupation of mineralocorticoid receptors in the distal kidney tubules is enhanced. The condition responds to administration of spironolactone, potassium supplementation, and discontinuation of licorice.
"The whole body 11bHSD1 activity reflects mainly hepatic expression. Initial studies that relied on measurements of cortisol-to-cortisone metabolites in urine (23,36) should be taken with caution as indicative of 11bHSD1 activity, because several other cortisol and cortisone metabolizing enzymes are deregulated in obesity (36). Of greater importance is the finding of reduced hepatic 11bHSD1 activity measured by the conversion of orally administered cortisone to cortisol (23,37). Thus, 11bHSD1 upregulation in obesity seems not to be a generalized process. In both the whole body and the splanchnic circulation there are no differences between obese and lean subjects regarding cortisol regeneration rates (as measured by [2H4]-cortisol tracer), presumably because an upregulation in adipose tissue is counterbalanced by a downregulation in the liver (15).
Biosynthesis of steroid hormones requires a battery of oxidative enzymes located in both mitochondria and endoplasmic reticulum. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. Within mitochondria, cholesterol is converted to pregnenolone by an enzyme in the inner membrane called CYP11A1. Pregnenolone itself is not a hormone, but is the immediate precursor for the synthesis of all of the steroid hormones. The following table delineates the enzymes required to synthesize the major classes of steroid hormones.