11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) enzymes catalyze the conversion of inert 11 keto-products (cortisone) to active cortisol, or vice versa, thus regulating the access of glucocorticoids to the steroid receptors. The human genome encodes two distinct HSD-11β isozymes (HSD-11β Type 1 and HSD-11β Type 2) on distinct genes. The dehydrogenase activity of a HSD-11β converts a 11beta-hydroxysteroid to the corresponding 11-oxosteroid by reducing NADP+ or NAD+. HSD-11βs are part of the larger class of oxidoreductases and HSD-11β Type 1 has oxidoreductase activity (the reverse of dehydrogenase activity). HSD-11βs participate in c21-steroid hormone metabolism and androgen and estrogen metabolism. Structural studies Several structures for HSD-11β Type 1 have been solved to date with various mutations and inhibitors. There are no known structures for HSD-11β Type 2. Function Cortisol, a glucocorticoid, binds the glucocorticoid receptor. However, because of its molecular similarity to aldosterone it also binds the mineralcorticoid receptor at higher concentrations. Both aldosterone and cortisol have a similar affinity for the mineralocorticoid receptor; however, there is vastly more cortisol in circulation than aldosterone. To prevent over-stimulation of the mineralocorticoid receptor by cortisol, HSD-11βs convert the biologically active cortisol to the inactive cortisone, which can no longer bind the mineralocorticoid receptor. HSD-11βs co-localizes with intracellular adrenal steroid receptors. Licorice, which contains glycyrrhizinic acid and enoxolone, can inhibit HSD-11β and lead to the apparent mineralocorticoid excess syndrome. Cortisol levels consequently rise, and cortisol binding to the mineralocorticoid receptor produces clinical signs and symptoms of hypokalemia, alkalosis and hypertension (i.e., mineralocorticoid excess). Isozymes In humans, there are two 11β-HSD isozymes: Clinical Application HSD-11βs are enzymes involved in steroid hormone physiology. HSD-11β Type 1 is found in metabolic tissues targeted by glucocorticoids and converts cortisone to active cortisol. HSD-11β Type 1 acts as a reductase producing active cortisol and the amplification of glucocorticoids. This enzyme is most abundant in the liver but can be found in most tissues in the body. HSD11B- Type 1 amplifies glucocorticoid concentrations in the liver and adipose tissue, glucocorticoid excess induces obesity with other features such as hypertension and diabetes mellitus. HSD-11β Type 2 is expressed by aldosterone-selective tissues and protects the mineralocorticoid receptor from the activation by cortisol by converting it to cortisone using the enzyme 11-Oxoreductase. HSD-11β Type 2 protects tissues from continuous activation by decreasing local cortisol levels and preventing 11-Oxoreductase from activating. In tissues that do not express the mineralocorticoid receptor, such as the placenta and