title: Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA reductase.
abstract: BACKGROUND
  Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR). There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR.
  
  
  METHODS
  39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2).
  
  
  RESULTS
  The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007). This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively.
  
  
  CONCLUSIONS
  Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, SE-14186 Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Gårevik
authors.forename: Cristine
authors.initials: C
authors.lastname: Skogastierna
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
authors.forename: Lena
authors.initials: L
authors.lastname: Ekström
mesh_terms: D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000008:administration & dosage / Q000009:adverse effects*; D002784:Cholesterol / Q000097:blood*; D004338:Drug Combinations; D020869:Gene Expression Profiling; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006937:Hypercholesterolemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000728:Androgens; D004338:Drug Combinations; D012333:RNA, Messenger; D013739:Testosterone; C036098:Testoviron-depot; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases