Hydroxysteroid dehydrogenase

About: Hydroxysteroid dehydrogenase is a research topic. Over the lifetime, 1087 publications have been published within this topic receiving 28468 citations. The topic is also known as: hydroxysteroid dehydrogenase.

Selective inhibition of 11-hydroxysteroid dehydrogenase 1 by 18-glycyrrhetinic acid but not 18-glycyrrhetinic acid

Abstract: Elevated cortisol concentrations have been associated with metabolic diseases such as diabetes type 2 and obesity. 11-hydroxysteroid dehydrogenase (11-HSD) type 1, catalyzing the conversion of inactive 11-ketoglucocorticoids into their active 11-hydroxy forms, plays an important role in the regulation of cortisol levels within specific tissues. The selective inhibition of 11-HSD1 is currently considered as promising therapeutic strategy for the treatment of metabolic diseases. In recent years, natural compound-derived drug design has gained considerable interest. 18-glycyrrhetinic acid (GA), a metabolite of the natural product glycyrrhizin, is not selective and inhibits both 11-HSD1 and 11-HSD2. Here, we compare the biological activity of 18-GA and its diastereomer 18-GA against the two enzymes in lysates of transfected HEK-293 cells and show that 18-GA selectively inhibits 11-HSD1 but not 11HSD2. This is in contrast to 18-GA, which preferentially inhibits 11-HSD2. Using a pharmacophore model based on the crystal structure of the GA-derivative carbenoxolone in complex with human 11HSD1, we provide an explanation for the differences in the activities of 18-GA and 18-GA. This model will be used to design novel selective derivatives of GA.

Alteration of 11β-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor by ethanol in rat liver and mouse hepatoma cells.

Abstract: Alcohol is a potential risk factor of type 2 diabetes, but its underlying mechanism is unclear. To explore this issue, Wistar rats and mouse hepatoma cells (Hepa 1–6) were exposed to ethanol, 8 g·kg −1·d −1 for 3 months and 100 mM for 48 h, respectively. Glucose and insulin tolerance tests in vivo were performed, and protein levels of 11 -hydroxysteroid dehydrogenase type 1 (11 -HSD1) and glucocorticoid receptor (GR) in liver and Hepa 1–6 cells were measured. Alterations of key enzymes of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase), as well as glycogen synthase kinase 3a (GSK3 α), were also examined. The results revealed that glucose levels were increased, and insulin sensitivity was impaired accompanied with liver injury in rats exposed to ethanol compared with controls. The 11 -HSD1, GR, PEPCK, G6Pase, and GSK3 α proteins were increased in the liver of rats treated with ethanol compared with controls. Ethanol-exposed Hepa 1–6 cells also showed higher expression of 11 -HSD1, GR, PEPCK, G6Pase, and GSK3 α proteins than control cells. After treatment of Hepa 1–6 cells exposed to ethanol with the GR inhibitor RU486, the expression of 11 -HSD1 and GR was significantly decreased. At the same time the increases in PEPCK, G6Pase, and GSK3 α levels induced by ethanol in Hepa 1–6 cells were also attenuated by RU486. The results indicate that ethanol causes glucose intolerance by increasing hepatic expression of 11 -HSD1 and GR, which leads to increased expression of gluconeogenic and glycogenolytic enzymes.

Histochemical Localization of Some Hydroxysteroid Dehydrogenases in the Mouse Epididymis

Abstract: The mouse epididymis was studied to localize histochemically a number of hydroxysteroid dehydrogenases in the various zones. The epithelium of the posterior half of the initial segment (head) and the anterior half of the middle segment (body) shows a strong reaction for △5-3β-, 3α,5α-, 3α,5β-, 11β-, 16α-, 170β- 20α- and 20β-hydroxysteroid dehydrogenases. This activity attenuates posteriorly. Only the 11β-hydroxysteroid dehydrogenase is present throughout the length of the epididymis. The luminal contents of the middle segment also show the histochemical utilization of a number of steroids.