scholarly journals Molecular and Enzymatic Characterizations of Novel Bifunctional 3β-Hydroxysteroid Dehydrogenases/C-4 Decarboxylases fromArabidopsis thaliana

2006 ◽  
Vol 281 (37) ◽  
pp. 27264-27277 ◽  
Author(s):  
Alain Rahier ◽  
Sylvain Darnet ◽  
Florence Bouvier ◽  
Bilal Camara ◽  
Martin Bard
Keyword(s):  
Hydroxysteroid Dehydrogenases

scholarly journals 11β-Hydroxysteroid dehydrogenases control access of 7β,27-dihydroxycholesterol to retinoid-related orphan receptor γ

2019 ◽  
Vol 60 (9) ◽  
pp. 1535-1546 ◽  
Author(s):  
Katharina R. Beck ◽  
Silvia G. Inderbinen ◽  
Sharavan Kanagaratnam ◽  
Denise V. Kratschmar ◽  
Anton M. Jetten ◽  
...  
Keyword(s):  
Orphan Receptor ◽  
Hydroxysteroid Dehydrogenases

scholarly journals Biochemical Factors Governing the Steady-State Estrone/Estradiol Ratios Catalyzed by Human 17β-Hydroxysteroid Dehydrogenases Types 1 and 2 in HEK-293 Cells

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4154-4162 ◽  
Author(s):  
Daniel P. Sherbet ◽  
Oleg L. Guryev ◽  
Mahboubeh Papari-Zareei ◽  
Dario Mizrachi ◽  
Siayareh Rambally ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Redox State ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Hydroxysteroid Dehydrogenase ◽  
Structural Features ◽  
Intact Cells ◽  
Hek 293 ◽  
Hydroxysteroid Dehydrogenases ◽  
293 Cells

Abstract Human 17β-hydroxysteroid dehydrogenase types 1 and 2 (17βHSD1 and 17βHSD2) regulate estrogen potency by catalyzing the interconversion of estrone (E1) and estradiol (E2) using nicotinamide adenine dinucleotide (phosphate) cofactors NAD(P)(H). In intact cells, 17βHSD1 and 17βHSD2 establish pseudo-equilibria favoring E1 reduction or E2 oxidation, respectively. The vulnerability of these equilibrium steroid distributions to mutations and to altered intracellular cofactor abundance and redox state, however, is not known. We demonstrate that the equilibrium E2/E1 ratio achieved by 17βHSD1 in intact HEK-293 cell lines is progressively reduced from 94:6 to 10:90 after mutagenesis of R38, which interacts with the 2′-phosphate of NADP(H), and by glucose deprivation, which lowers the NADPH/NADP+ ratio. The shift to E2 oxidation parallels changes in apparent Km values for purified 17βHSD1 proteins to favor NAD(H) over NADP(H). In contrast, mutagenesis of E116 (corresponding to R38 in 17βHSD1) and changes in intracellular cofactor ratios do not alter the greater than 90:10 E1/E2 ratio catalyzed by 17βHSD2, and these mutations lower the apparent Km of recombinant 17βHSD2 for NADP(H) only less than 3-fold. We conclude that the equilibrium E1/E2 ratio maintained by human 17βHSD1 in intact cells is governed by NADPH saturation, which is strongly dependent on both R38 and high intracellular NADPH/NADP+ ratios. In contrast, the preference of 17βHSD2 for E2 oxidation strongly resists alteration by genetic and metabolic manipulations. These findings suggest that additional structural features, beyond the lack of a specific arginine residue, disfavor NADPH binding and thus support E2 oxidation by 17βHSD2 in intact cells.

HYDROXYSTEROID DEHYDROGENASES IN NORMAL AND ABNORMAL HUMAN TESTES

1966 ◽  
Vol 35 (3) ◽  
pp. 239-NP ◽  
Author(s):  
A. H. BAILLIE ◽  
W. S. MACK
Keyword(s):  
Similar Pattern ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Colour Reaction ◽  
Adult Human ◽  
Hydroxysteroid Dehydrogenases

SUMMARY 3α-, 3β-, 11β-, 16β-, 17β- and 20β-hydroxysteroid dehydrogenases have been localized histochemically in the Leydig cells of prepubertal and adult human testes; 3α-, 16β- and 17β-hydroxysteroid dehydrogenases were present in the seminiferous tubules also. A similar pattern was found in cryptorchid testes. In addition 3β-sulphoxy steroids, including DHA sulphate, gave a good colour reaction in human Leydig cells. Testes from oestrogen-treated subjects had no histochemically demonstrable hydroxysteroid dehydrogenases and this applied also to infarcted testes. Testes from a case of Klinefelter's syndrome were found to lack 17β- and 20β-hydroxysteroid dehydrogenases in the Leydig cells. The biochemical significance of these results is discussed.

Novel 18β-glycyrrhetinic acid analogues as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenases

2004 ◽  
Vol 12 (16) ◽  
pp. 4439-4457 ◽  
Author(s):  
Xiangdong Su ◽  
Harshani Lawrence ◽  
Dharshini Ganeshapillai ◽  
Adrian Cruttenden ◽  
Atul Purohit ◽  
...  
Keyword(s):  
Glycyrrhetinic Acid ◽  
Selective Inhibitors ◽  
Hydroxysteroid Dehydrogenases

Genetic manipulation of 11β-hydroxysteroid dehydrogenases in mice

2005 ◽  
Vol 289 (3) ◽  
pp. R642-R652 ◽  
Author(s):  
Janice M. Paterson ◽  
Jonathan R. Seckl ◽  
John J. Mullins
Keyword(s):  
Genetic Manipulation ◽  
Receptor Activation ◽  
Regulation Of Expression ◽  
Dynamic Regulation ◽  
Temporal Regulation ◽  
Hydroxysteroid Dehydrogenases ◽  
Corticosteroid Receptor ◽  
Health And Disease ◽  
Restricted Pattern

11β-Hydroxysteroid dehydrogenases (HSDs) interconvert active 11-hydroxy glucocorticoids (cortisol, corticosterone) and their inert 11-keto derivatives (cortisone, 11-dehydrocorticosterone). 11β-HSD type 1 is a predominant reductase that regenerates active glucocorticoids in expressing cells, thus amplifying local glucocorticoid action, whereas 11β-HSD type 2 catalyzes rapid dehydrogenation, potently inactivating intracellular glucocorticoids. Both isozymes thus regulate receptor activation by substrate availability. Spatial and temporal regulation of expression are important determinants of the physiological roles of 11β-HSDs, with each isozyme exhibiting a distinct, tissue-restricted pattern together with dynamic regulation during development and in response to environmental challenges, including diet and stress. Transgenic approaches in the mouse have contributed significantly toward an understanding of the importance of these prereceptor regulatory mechanisms on corticosteroid receptor activity and have highlighted its potential relevance to human health and disease. Here we discuss current ideas of the physiological roles of 11β-HSDs, with emphasis on the key contributions made by studies of 11β-HSD gene manipulation in vivo.

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