Mineralocorticoid receptor metabolic effects

The mineralocorticoid aldosterone is also produced by the adrenal cortex and promotes retention of H20 and Na+ and loss of K+ by the kidney. Cortisol is also an agonist of the aldosterone receptor but the level of cortisol is kept low by type 2 11 (Thydroxysteroid dehydrogenase, which converts cortisol to the inactive cortisone (11-dehydrocortisol). Accordingly inhibition of this enzyme by 18(i>-glycyrrhetinic acid (from liquorice) elevates cortisol with consequent effects of H20 and Na+ retention, oedema and hypertension. Further potential sites of interference by plant substances with steroid hormone metabolism include enzymes involved in steroid hormone synthesis such as the cytochrome P450-linked 11 -hydroxylase that catalyses the last step of corticosterone synthesis. 

The mineralocorticoid properties of carbenoxolone are probably exerted by displacement of aldosterone from non-specific receptor sites in cells, thus making it more available to affect mineral metabolism. What this means in practice is that in normal doses carbenoxolone can cause salt and water retention, with occasional hypokalemia. These effects are common but usually mUd they are detected more often during treatment if patients are weighed, their blood pressure measured, and serum potassium concentrations checked. Those who take prolonged courses, elderly patients, and those with hepatic, cardiac, or renal impairment are at special risk severe effects, with serious hypertension, heart failure, and hypokalemia of sufficient degree to induce myopathy and tubular necrosis, can usually be ascribed to ill-advised treatment of people in whom carbenoxolone is contraindicated, to its use in elderly patients, or to prolonged intake without supervision. 

Corticosteroids traditionally are divided into mineralocorticoids and glucocorticoids according to their relative potencies in Na retention and effects on carbohydrate metabolism i.e., hepatic deposition of glycogen and gluconeogenesis) In general, potencies of steroids to sustain life in adrenalectomized animals closely parallel their mineralocorticoid activity, while potencies as antiinflammatory agents closely parallel their effects on glucose metabolism. The effects on Na" retention and the carbohydrate/anti-inflammatory actions are not closely related and reflect selective actions at distinct receptors. 

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