Document Detail


The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion.
MedLine Citation:
PMID:  9408083     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the distribution of the neurosteroids pregnenolone (Pe) and pregnenolone sulfate (PeS) in seven brain regions, and plasma and fat tissues in male adult rats following the intravenous infusion of 14 mg/kg Pe and 18 mg/kg PeS, respectively. After chromatographic separation of steroid sulfate esters and non-conjugated steroids by solid phase octadecyl C18 columns and celite column chromatographic separation of Pe from cross-reacted steroids, the concentrations of Pe and PeS were determined by radioimmunoassay. We found that both Pe and PeS concentrations were significantly increased in plasma, fat and brain compared to the vehicle controls after i.v. infusion of Pe and PeS. In the controls, Pe concentrations were highly correlated within brain regions and between fat and brain regions. Most correlations were lost after Pe and PeS infusions. The content of Pe and PeS was not uniformly distributed in the brain. The hypothalamus contained the highest level of Pe in controls, Pe-infused and PeS-infused rats (12 +/- 3.1, 3500 +/- 180 and 590 +/- 54 ng/g, respectively). The highest concentration of PeS was detected in the hypothalamus (26 +/- 8.2 ng/g) and striatum (17 +/- 4.1 ng/g) in controls, in the hypothalamus (200 +/- 24 ng/g) after PeS infusion as well as in the hypothalamus and medulla oblongata (57 +/- 9.6 and 55 +/- 7.6 ng/g, respectively) after Pe infusion. This study has yielded evidence that PeS injected i.v. can cross the blood-brain barrier without being hydrolysed to the more lipophilic Pe, and can thus be taken up by the brain.
Authors:
M D Wang; G Wahlström; T Bäckström
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  62     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1998-01-13     Completed Date:  1998-01-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  299-306     Citation Subset:  IM    
Affiliation:
Department of Physiology, Umeå, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blood-Brain Barrier
Brain / drug effects,  metabolism*
Hypothalamus / drug effects,  metabolism*
Infusions, Intravenous
Male
Pregnenolone / blood,  pharmacokinetics*
Rats
Rats, Sprague-Dawley
Steroids / metabolism,  pharmacology
Tissue Distribution
Chemical
Reg. No./Substance:
0/Steroids; 1247-64-9/pregnenolone sulfate; 145-13-1/Pregnenolone

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


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