Document Detail


Progestins block cholesterol synthesis to produce meiosis-activating sterols.
MedLine Citation:
PMID:  11259396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The resumption of meiosis is regulated by meiosis-preventing and meiosis-activating substances in testes and ovaries. Certain C29 precursors of cholesterol are present at elevated levels in gonadal tissue, but the mechanism by which these meiosis-activating sterols (MAS) accumulate has remained an unresolved question. Here we report that progestins alter cholesterol synthesis in HepG2 cells and rat testes to increase levels of major MAS (FF-MAS and T-MAS). These C29 sterols accumulated as a result of inhibition of Delta24-reduction and 4alpha-demethylation. Progesterone, pregnenolone, and 17alpha-OH-pregnenolone were potent inhibitors of Delta24-reduction in an in vitro cell assay and led to the accumulation of desmosterol, a Delta5,24 sterol precursor of cholesterol. A markedly different effect was observed for 17alpha-OH-progesterone, which caused the accumulation of sterols associated with inhibition of 4alpha-demethylation. The flux of 13C-acetate into lathosterol and cholesterol was decreased by progestins as measured by isotopomer spectral analysis, whereas newly synthesized MAS accumulated. The combined evidence that MAS concentrations can be regulated by physiological levels of progestins and their specific combination provides a plausible explanation for the elevated concentration of MAS in gonads and suggests a new role for progestins in fertility.
Authors:
B Lindenthal; A L Holleran; T A Aldaghlas; B Ruan; G J Schroepfer; W K Wilson; J K Kelleher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  15     ISSN:  0892-6638     ISO Abbreviation:  FASEB J.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-03-22     Completed Date:  2001-04-19     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  775-84     Citation Subset:  IM    
Affiliation:
Department of Physiology and Experimental Medicine, The George Washington University School of Medical and Health Sciences, Washington, DC 20037, USA. bernard.lindenthal@schering.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight
Cholestadienols / metabolism,  pharmacology*
Cholesterol / biosynthesis*,  metabolism
Estrogen Antagonists / pharmacology
Humans
Hydroxyprogesterones / metabolism,  pharmacology
Male
Meiosis / physiology
Miconazole / pharmacology
Mifepristone / pharmacology
Progestins / metabolism,  pharmacology*
Rats
Spectrum Analysis
Sterols / biosynthesis*
Tamoxifen / pharmacology
Testis / cytology,  drug effects*,  metabolism
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
DK-45164/DK/NIDDK NIH HHS; HL-49122/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cholestadienols; 0/Estrogen Antagonists; 0/Hydroxyprogesterones; 0/Progestins; 0/Sterols; 10540-29-1/Tamoxifen; 22916-47-8/Miconazole; 57-88-5/Cholesterol; 84371-65-3/Mifepristone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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