Endocrine Abstracts (2006) 11 P404

Testosterone replacement reduces aortic fatty streak formation in testosterone deficient Tfm mice following feeding on a cholesterol-enriched diet

JE Nettleship1, RD Jones1, CM Biggins2, KS Channer2 & TH Jones1


1University of Sheffield, Sheffield, United Kingdom; 2Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.


We have previously shown that Tfm mice which have a non-functional androgen receptor (AR) and low endogenous levels of testosterone exhibit increased fatty streak formation within the aortic root. The aim of the present study was to administer varying degrees of testosterone to these animals in comparison to littermate controls to determine the role of the AR in the anti-atherogenic action of testosterone.

Eight-week-old Tfm mice (n=24) and XY littermates (n=16) were placed into 5 groups which received a fortnightly 10 μl i.m injection of either saline, Sustanon100 (S100) or Sustanon250 (S250). At ten weeks of age all mice were fed a cholesterol-enriched diet for 28-weeks. Mice were sacrificed, the hearts perfused with saline and frozen at −80°C. Five, 8 micrometre cryosections were taken at 100 micrometre intervals through the aortic root of each heart. Sections were stained with oil red O and counterstained with haematoxylin and lipid-stained areas quantified via digital analysis, and expressed as percentage of medial area.

Table 1
AR/Testosterone StatusLipid Deposition (% medial area)
Tfm – salineAR deficient/low testosterone2.86 (0.39)
XY – salineAR intact/physiological testosterone0.44 (0.09)
Tfm – S100AR deficient/physiological testosterone0.37 (0.14)a
Tfm – S250AR deficient/supra-physiological testosterone1.25 (0.20)a,b
XY – S250AR intact/supra-physiological testosterone0.22 (0.17)
aP<0.001 versus Tfm – saline, bP<0.05 versus Tfm – S100

Aortic fatty-streak formation is significantly reduced in AR-deficient Tfm mice receiving physiological testosterone replacement and to a lesser extent supra-physiological testosterone therapy. Testosterone induces anti-atherogenic effects via a non-genomic mechanism.

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