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.

Syndrome of alopecia totalis and 17b-hydroxysteroid dehydrogenase deficiency.

Abstract: A distinct and previously undescribed syndrome of alopecia totalis, ichthyosis, and male pseudohermaphroditism due to steroid 17b-hydroxysteroid dehydrogenase deficiency was observed in an Israeli-Arab newborn infant.

Single nucleotide polymorphisms of 17β-hydroxysteroid dehydrogenase type 7 gene: Mechanism of estramustine-related adverse reactions?

Abstract: Objectives: To investigate the influence of single nucleotide polymorphisms (SNP) on transcription of the 17β-hydroxysteroid dehydrogenase (HSD17B7) gene. Methods: Luciferase reporter genes containing a 5′-flanking of the HSD17B7 gene, as well as the sequence around the SNP, were transfected into LNCaP and DU145 cells. Then, luciferase assays were carried out. Results: The presence of the G allele resulted in an increase of transcriptional activity derived from the 5′-flanking region of the HSD17B7 gene by 270% and 370% in LNCaP and DU145 cells, respectively. Transcriptional activity of the HSD17B7 gene containing the G allele was higher than that of the C allele. Conclusions: The transcriptional activity of the HSD17B7 gene containing the G allele is higher than that of the C allele. This difference in HSD17B7 expression may regulate the risk of peripheral edema as an adverse reaction induced by estramustine phosphate sodium.

Method to identify modulators for human 3alpha-hydroxysteroid dehydrogenase

Abstract: 3 α-hydroxysteroid dehydrogenase (3a-HSD) plays a central role in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The high resolution structure of human type III 3a-HSD crystallized in complex with cofactor NADP is determined by X-ray diffraction. Furthermore the active site is determined. The structure coordinates of the enzyme may be used to design and select novel classes of modulators to human type III 3a-HSD.

Design, synthesis, molecular docking and in vitro evaluation of benzothiazole derivatives as 11β-hydroxysteroid dehydrogenase type 1 inhibitors

Abstract: 11-Beta hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates cortisol levels mainly in adipose, hepatic and brain tissues. There is a relationship between the high activity of this enzyme and the development of obesity and metabolic disorders. The inhibition of 11β-HSD1 has been shown to attenuate the development of type 2 diabetes mellitus, insulin resistance, metabolic syndrome and other diseases mediated by excessive cortisol production. In this work, fifteen benzothiazole derivatives substituted with electron-withdrawing and electron-donating groups were designed to explore their affinity for 11β-HSD1 using in silico methods. The results show that (E)-5-((benzo[d]thiazol-2-ylimino)(methylthio)methylamino)-2-hydroxybenzoic acid (C1) has good physicochemical properties and favorable interactions with 11β-HSD1 through hydrogen bonding and hydrophobic interactions in the catalytic site formed by Y183, S170 and Y177. Furthermore, C1 was synthesized and evaluated in vitro and ex vivo using clobenzorex (CLX) as a reference drug in obese Zucker rats. The in vitro results showed that C1 was a better inhibitor of human 11β-HSD1 than CLX. The ex vivo assay results demonstrated that C1 was capable of reducing 11β-HSD1 overexpression in mesenteric adipose tissue. Therefore, C1 was able to decrease the activity and expression of 11β-HSD1 better than CLX.

A novel steroid inhibitor for a rat 20α-hydroxysteroid dehydrogenase isozyme

Abstract: 20alpha-Hydroxysteroid dehydrogenase (20alpha-HSD, E.C.1.1.1.149) in rat luteal tissue, which catalyzes conversion of progesterone to a biologically inactive steroid, 20alpha-hydroxypregn-4-ene-3-one (20alpha-OHP), suppresses progesterone secretion into the circulation. An increase in 20alpha-HSD activity in luteal tissue in rats is a prerequisite for functional corpus luteum regression. This study was undertaken to find a steroid inhibitor for ovarian cytosolic 20alpha-HSD activity among derivatives based on progesterone structure. A derivative designated as STZ26 (D-homo-16-oxa-4-androstene-3,16alpha-dione) was found to inhibit potently 20alpha-HSD activity in cultured luteal cells. Ovarian 20alpha-HSD activity consists of two isoforms (HSD1 and HSD2). Kinetic analyses of STZ26 for HSD1 and HSD2 showed that the compound suppressed only HSD1 activity by competitive inhibition. Pseudopregnant rats were treated with STZ26 from 13 to 19 days after cervical stimulation. Either an elevation of peripheral 20alpha-OHP levels or a concomitant depletion of peripheral progesterone levels at the end of pseudopregnancy was considerably inhibited in treated animals, although not completely. The results showed that STZ26 is a biologically active inhibitor for HSD1 activity in the luteal tissue and suggested that the depletion of progesterone levels toward the end of pseudopregnancy is not solely due to the elevation of HSD1 activity.