Document Detail


Endogenous selective inhibitors of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2 of adrenal origin.
MedLine Citation:
PMID:  16188377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In earlier studies [Latif, S.A., Sheff, M.F., Ribeiro, C.E., Morris, D.J., 1997. Selective inhibition of sheep kidney 11beta-hydroxysteroid-dehydrogenase isoform 2 activity by 5alpha-reduced (but not 5beta) derivatives of adrenocorticosteroids. Steroids 62, 230-237], only derivatives of steroid hormones possessing the 5alpha-Ring A-reduced configuration selectively inhibited 11beta-HSD2-dehydrogenase, whereas their 5beta-derivatives were inactive. This present study focuses on an expanded group of endogenous 11-oxygenated, 5alpha and 5beta-Ring A-reduced metabolites of adrenocorticosteroids, and progestogen and androgen steroid hormones. These substances were tested for their inhibitory properties against 11beta-HSD2, 11beta-HSD1-dehydrogenase and 11beta-HSD1 reductase. The present studies showed that the following compounds stand out as potent inhibitors. These are 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone, 11beta-OH-progesterone, 11beta-OH-allopregnanolone, 11beta-OH-testosterone, and 11beta-OH-androstanediol, inhibitors of 11beta-HSD1-dehydrogenase; 3alpha,5alpha-TH-11-dehydro-corticosterone, 11-keto-progesterone, 11-keto-allopregnanolone, and 11-keto-3beta,5alpha-TH-testosterone, inhibitors of 11beta-HSD1 reductase; 3alpha,5alpha-TH-aldosterone, 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone,11-dehydro-corticosterone, 3alpha,5alpha-TH-11-dehydro-corticosterone, 11beta-OH-progesterone, 11-keto-progesterone, 11beta-OH-allopregnanolone, 11-keto-allopregnanolone, 11beta-OH-testosterone, and 11-keto-testosterone, inhibitors of 11beta-HSD2. All of these substances have the potential to be derived from adrenally synthesized corticosteroids. Substances with similar structures to those described may help in the design of exogenous agents for the management of a variety of disease states involving 11beta-HSD isoenzymes.
Authors:
Syed A Latif; Hector A Pardo; Matthew P Hardy; David J Morris
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-09-26
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  243     ISSN:  0303-7207     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-15     Completed Date:  2006-03-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  43-50     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, The Miriam Hospital, Brown University Medical School, 164 Summit Avenue, Providence, RI 02906, USA. slatif@lifespan.org
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*,  metabolism
11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors*,  metabolism
Adrenal Glands / metabolism*
Animals
Isoenzymes / antagonists & inhibitors,  metabolism
Leydig Cells / enzymology
Male
Microsomes / enzymology
Rats
Sheep
Steroids / metabolism*,  pharmacology
Grant Support
ID/Acronym/Agency:
HD33000/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Steroids; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 1; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2

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