11β-Hydroxysteroid dehydrogenase type 1, also known as cortisone reductase, is an

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADP ...

-dependent

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

highly expressed in key metabolic tissues including

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

, adipose tissue, and the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. In these tissues, HSD11B1 reduces

cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the ...

to the active hormone

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the '' zona fasciculata'' of the adrenal cortex in the adrenal g ...

that activates glucocorticoid receptors. It belongs to the family of short-chain dehydrogenases. It is encoded by the

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone

to the inactive

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

, and a particular variation in this gene has been associated with obesity and

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood suga ...

in children. Two transcript variants encoding the same protein have been found for this gene. Cortisol-cortisone en

Clinical significance

11β-HSD1 is inhibited by

carbenoxolone Carbenoxolone (CBX) is a glycyrrhetinic acid derivative with a steroid-like structure, similar to substances found in the root of the licorice plant. Carbenoxolone is used for the treatment of peptic, esophageal and oral ulceration and inflamma ...

, a drug typically used in the treatment of

peptic ulcer Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...

s. Moreover, 18alpha-

glycyrrhizic acid Glycyrrhizin (or glycyrrhizic acid or glycyrrhizinic acid) is the chief Sweetness, sweet-tasting constituent of ''Glycyrrhiza glabra'' (liquorice) root. Structurally, it is a saponin used as an emulsion, emulsifier and gel-forming agent in foods ...

from the root of ''

glycyrrhiza glabra Liquorice (British English) or licorice (American English) ( ; also ) is the common name of ''Glycyrrhiza glabra'', a flowering plant of the bean family Fabaceae, from the root of which a sweet, aromatic flavouring can be extracted. The liq ...

'' was discovered as an inhibitor. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes.

Epigallocatechin gallate Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG – the most abundant catechin in tea – is a polyphenol under basic research for it ...

from

green tea Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since ...

can also potently inhibit this enzyme; green tea is a complex mixture of various phenolics with contents varying with production and processing, and some of the phenolics are known HDAC inhibitors that alter genetic expression. EGCG as usually consumed in green tea is poorly absorbed into the bloodstream. More research is needed to reach firm conclusions.

Function

Clinical significance

See also

References

External links

Further reading