11 P-Hydroxysteroid Dehydrogenase Type

Another example of a GeMM transgenic model displaying clinical like conditions including cardiac hypertrophy, fibrosis, and heart failure is the a-myosin heavy chain promoter 11 p-hydroxysteroid dehydrogenase type 2 transgenic mouse (18). Eplerenone (INSPRA , Pfizer Inc.), a selective aldosterone blocker, was tested in this model and proved to ameliorate the phenotype. This model revealed the deleterious consequences of inappropriate mineralocorticoid receptor activation in the heart and supported the notion that aldosterone blockade may provide additional therapeutic benefit in the treatment of heart failure. 

Hexose 6-phosphate dehydrogenase and 11 p-hydroxysteroid dehydrogenase type 1... 

E, White PC, Hewison M, Mason PJ, Connell JM, Shackleton CH, 49. Stewart PM. Mutations in the genes encoding 11 P-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat. Genet. 50. 2003 34 434-439. 

Lack of association of the 11 P-hydroxysteroid dehydrogenase type 53. 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen... 

Lavery GG, Walker EA, Draper N, Jeyasuria P, Marcos J, Shackleton CH, Parker KL, White PC, Stewart PM. Hexose-6-phosphate dehydrogenase knock-out mice lack 11 P-hydroxysteroid dehydrogenase type 1-mediated glucocorticoid generation. J. Biol. Chem. 2006 281 6546-6551. 

Hewitt KN, Walker EA, Stewart PM. Minireview hexose-6-phosphate dehydrogenase and redox control of 11 P-hydroxysteroid dehydrogenase type 1 activity. Endocrinology 2005 146 2539-2543. 

Lim WKA, Ton SH, Khahd BAK (2009) 11 P-hydroxysteroid dehydrogenase type 1 and 2 in orally administered glycyrrhizic acid-treated rats fed on high-fat diet. Abstract Pg 94 34th annual conference Malaysian Society for Biochemistry and Molecular Biology, 3rd ASEAN Biochemistry conference... 

Fig. 25 Mouse liver microsome (MLM) half-life data for piperidine-based 11 P-hydroxysteroid dehydrogenase type I (lip-HSDl) inhibitors...

Monoester 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-l-carboxylic acid 59 (Figure 4.17) is a building block of many potential therapeutic candidates for inhibitors of 11-p-hydroxysteroid dehydrogenase type 1 enzyme and their use in the treatment of non-insulin-dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and CNS disorders. It is also required for the synthesis of 5-hydroxytryptamine receptor agonists, useful for the treatment of anxiety disorders and schizophrenia [90,91]. 

Chrousos, G. P. Is 11-beta-hydroxysteroid dehydrogenase type 1 a good therapeutic target for blockade of glucocorticoid actions Proc. Natl. Acad. Sci. USA 2004, 101, 6329-6330. 

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