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The mouse with the humanized liver: a new model for metabolic studies of anabolic steroids in man

Leen Lootens UGent (2010)
abstract
The uPA+/+-SCID mouse with a humanized liver is evaluated as an in vivo model to study steroid metabolism. This small animal model is used to find urinary markers that allow for the detection of steroid abuse. This is of great benefit to the scientific doping community, because steroids are prohibited by WADA and are still amongst the most frequently detected doping substances. Steroids are extensively metabolized in the liver and normally excretion studies are best performed in humans to determine which metabolites are detectable after steroid intake. But this experimental approach raises a lot of ethical concerns to use healthy human volunteers. As an alternative, in vitro cell cultures are used to have an indication on the steroid metabolism. However, most primary cell cultures have a very limited lifespan. To circumvent the above stated problems, an in vivo chimeric mouse model was presented. These mice are transplanted with human hepatocytes, since the metabolism is different in mice and humans, combined with the fact that the liver is the main organ for metabolic transformations. To verify the comparability between the chimeric mice and humans, several administration studies with androst-4-ene-3,17-dione, methandienone and 19-norandrost-4-ene-3,17-dione were performed. These excretion studies have demonstrated that the steroids administered to the humanized mice underwent approximately the same metabolic transformations as previously described in humans. Hence these results prove that the mouse model can serve as a complementary alternative for human steroid excretion studies or in vitro hepatocytes cultures. To further illustrate the applicability of the chimeric mice, the results of an integrated strategy are included where data of human and chimeric mice are combined to discover new and/or longer detectable steroid metabolites.
Please use this url to cite or link to this publication:
author
promoter
UGent and UGent
organization
year
type
dissertation (monograph)
subject
keyword
Doping, mouse urine, metabolism, GC-MS, steroids, LC-MS/MS
pages
173 pages
publisher
Ghent University. Faculty of Medicine and Health Sciences
place of publication
Ghent, Belgium
defense location
Zwijnaarde : Technologiepark (deVGen-gebouw)
defense date
2010-05-07 16:00
ISBN
9789490695279
language
English
UGent publication?
yes
classification
D1
additional info
dissertation consists of copyrighted materials
copyright statement
I have transferred the copyright for this publication to the publisher
id
947631
handle
http://hdl.handle.net/1854/LU-947631
alternative location
http://lib.ugent.be/fulltxt/RUG01/001/394/982/RUG01-001394982_2010_0001_AC.pdf
date created
2010-05-18 09:40:02
date last changed
2010-05-20 14:42:50
@phdthesis{947631,
  abstract     = {The uPA+/+-SCID mouse with a humanized liver is evaluated as an in vivo model to study steroid metabolism. This small animal model is used to find urinary markers that allow for the detection of steroid abuse. 
This is of great benefit to the scientific doping community, because steroids are prohibited by WADA and are still amongst the most frequently detected doping substances. Steroids are extensively metabolized in the liver and normally excretion studies are best performed in humans to determine which metabolites are detectable after steroid intake. But this experimental approach raises a lot of ethical concerns to use healthy human volunteers. As an alternative, in vitro cell cultures are used to have an indication on the steroid metabolism. However, most primary cell cultures have a very limited lifespan. 
To circumvent the above stated problems, an in vivo chimeric mouse model was presented. These mice are transplanted with human hepatocytes, since the metabolism is different in mice and humans, combined with the fact that the liver is the main organ for metabolic transformations. To verify the comparability between the chimeric mice and humans, several administration studies with androst-4-ene-3,17-dione, methandienone and 19-norandrost-4-ene-3,17-dione were performed. These excretion studies have demonstrated that the steroids administered to the humanized mice underwent approximately the same metabolic transformations as previously described in humans. 
Hence these results prove that the mouse model can serve as a complementary alternative for human steroid excretion studies or in vitro hepatocytes cultures. To further illustrate the applicability of the chimeric mice, the results of an integrated strategy are included where data of human and chimeric mice are combined to discover new and/or longer detectable steroid metabolites.},
  author       = {Lootens, Leen},
  isbn         = {9789490695279},
  keyword      = {Doping,mouse urine,metabolism,GC-MS,steroids,LC-MS/MS},
  language     = {eng},
  pages        = {173},
  publisher    = {Ghent University. Faculty of Medicine and Health Sciences},
  school       = {Ghent University},
  title        = {The mouse with the humanized liver: a new model for metabolic studies of anabolic steroids in man},
  url          = {http://lib.ugent.be/fulltxt/RUG01/001/394/982/RUG01-001394982\_2010\_0001\_AC.pdf},
  year         = {2010},
}

Chicago
Lootens, Leen. 2010. “The Mouse with the Humanized Liver: a New Model for Metabolic Studies of Anabolic Steroids in Man”. Ghent, Belgium: Ghent University. Faculty of Medicine and Health Sciences.
APA
Lootens, Leen. (2010). The mouse with the humanized liver: a new model for metabolic studies of anabolic steroids in man. Ghent University. Faculty of Medicine and Health Sciences, Ghent, Belgium.
Vancouver
1.
Lootens L. The mouse with the humanized liver: a new model for metabolic studies of anabolic steroids in man. [Ghent, Belgium]: Ghent University. Faculty of Medicine and Health Sciences; 2010.
MLA
Lootens, Leen. “The Mouse with the Humanized Liver: a New Model for Metabolic Studies of Anabolic Steroids in Man.” 2010 : n. pag. Print.