11β-Hydroxysteroid dehydrogenase

11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) enzymes catalyze the conversion of inert 11 keto-products (cortisone) to active cortisol, or vice versa,[1] thus regulating the access of glucocorticoids to the steroid receptors.

HSD-11β Type 1 is found in metabolic tissues targeted by glucocorticoids and converts cortisone to active cortisol.

[7] 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.

[6] In tissues that do not express the mineralocorticoid receptor, such as the placenta and testis, it protects cells from the growth-inhibiting and/or pro-apoptotic effects of cortisol, particularly during embryonic development.

[8] Since the main functions of HSD-11βs are for the regulation of glucocorticoids, the two isozymes are linked to various overstimulation or depletion of glucocorticosteroids that result in chemical imbalances in the human body.

[9] Cushing's Disease, synonymous with hypercortisolism, involves overwhelming the cortisol-neutralizing ability of 11β-HSD2 with high concentrations of cortisol.

[10] This allows cortisol to outcompete aldosterone and bind to mineralocorticoid receptors, resulting in the activation of several pathways that increase blood pressure.

[12] The type 2 isozyme converts active glucocorticoid hormones to inactive metabolites in target tissues such as kidney, salivary glands, intestines, etc.

[12] The activation of the two isozymes of HSD-11β in the kidneys and liver triggers the extra-adrenal formation in alloxan diabetes, which affiliates with the reduction in the synthesis of glucocorticoid hormones in the adrenal glands.

[12] Thus, inhibitors of HSD-11β Type 1 can serve as a potential treatment agents for diabetes mellitus, obesity, and metabolic syndrome by decreasing production of active glucocorticoids.

[13] Some consequences of a high expression HSD-11β Type 2 are anxiety and cardiometabolic disorders, both of which are part of the early age glucocorticoid programming.

[14] The reason for this is because the HSD-11β Type 2 is meant to be expressed in high quantities in the placenta, This is so because the enzymes secure the fetus from exposure to increased levels of glucocorticoids, which are linked to underweight newborns.