11-Beta hydroxysteroid dehydrogenase

11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) is the name of a family of enzymes that 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.

Cortisone

Cortisol. Note the OH at the 11 position on ring C. (The other differences between the diagrams are not of consequence.)

Function

Cortisol, a glucocorticoid, binds the glucocorticoid receptor. However, because of its molecular similarity to aldosterone it is also capable of binding the mineralcorticoid receptor. 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-11β converts the biologically active cortisol to the inactive cortisone, which can no longer bind to the mineralocorticoid receptor. HSD-11β co-localizes with intracellular adrenal steroid receptors. Licorice or Carbenoxolone , which contains glycyrrhetinic acid, can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.

Isoforms

In humans, there are two HSD11B isoforms:

HSD11B1	NADPH-dependent	Highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system.	In these tissues, HSD11B1 reduces cortisone to the active hormone cortisol that activates glucocorticoid receptors.
HSD11B2	NAD+-dependent	Expressed in aldosterone-selective tissues,including colon, salivary glands, and placenta.	In these tissues, HSD11B2 oxidizes cortisol to cortisone and prevents illicit activation of the mineralocorticoid receptor.

Inhibition of HSD11B1 has been suggested as a possible therapy for treatment of obesity and metabolic syndrome.

See also

• 11β-hydroxysteroid dehydrogenase type 1
• 11beta-hydroxysteroid dehydrogenase

External links

• MeSH 11-beta-Hydroxysteroid+Dehydrogenases