11β-Гидроксистероиддегидрогеназы: регуляция глюкокортикоидов и влияние на развитие плода.

Class of enzymes
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.

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.

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 overstimulation 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).

HSD 11βs are active in organs and in the adrenal gland. The two isoenzymes take on various duties. It is essential in Hypothalamo Pituitary Adrenal Axis function. The presence of glucocorticoids has contributed to the relatively low infant birth weight. A decrease in HSD 11β Type 2 in the placenta can lead to infant restriction in growth, specifically during the first 12 months of an infant's life. 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.