title: [Effect of physiological doses of testosterone on mitochondrial DNA deletion in castrated mice].
abstract: OBJECTIVE
  To evaluate the effect of physiological doses of testosterone on mitochondrial DNA (mtDNA) deletion in the aortic vascular wall of castrated C57BL/6J mice.
  
  
  METHODS
  Twenty-four male C57BL/6J mice were randomized into normal control group (n=8), castrated+placebo group (castrated group, n=8), and castrated+physiological doses (1 mg/kg every 3 days) of testosterone group (n=8). The mice were fed normally for 3 months along with 8 mice with natural aging (18 months old), after which blood samples were obtained from all the groups for measurement of testosterone concentrations. The aortic mtDNA was extracted to analyze the deleted fragments using nested PCR, and fragments with deletions were purified and identified by sequence analysis.
  
  
  RESULTS
  Compared with the normal control group, the castrated group showed a significantly higher optical density ratio of the deletions [(18.1713 ∓ 2.4317)% vs (36.8475 ∓ 3.3365)%], but no significant difference was found between the castrated and natural ageing group [(42.3075 ∓ 3.6556)%]. The castrated+testosterone showed a lowered optical density ratio of (23.6488 ∓ 2.7634)% as compared with the castrated and natural ageing group, but a similar one with the normal control group. Sequence analysis identified 4 different types of deletions in the aging aorta at 3713, 3864, 4236, and 4415 bp, and the presence of direct repeats was confirmed to flank the deletions.
  
  
  CONCLUSIONS
  Multiple mtDNA deletions occur in ageing mice at a higher rate than in young mice. Testosterone deficiency is associated with increased aortic mtDNA deletions, which can be decreased by physiological doses of testosterone.
authors.affiliation: Department of Cardiology, Nanfang Hospotal, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Sai-zhu
authors.initials: SZ
authors.lastname: Wu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Hong
authors.forename: Wen-yan
authors.initials: WY
authors.lastname: Lai
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D011897:Random Allocation; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D004272:DNA, Mitochondrial; D013739:Testosterone