Endocrine Abstracts

Introduction: Low endogenous testosterone is associated with atherosclerosis in elderly men. The aim of this study was to determine whether an inactive androgen receptor (AR) coupled with testosterone deficiency, inherent to the testicular feminised (Tfm) mouse, is associated with atherosclerosis following cholesterol feeding.

Methods: Eight-week-old Tfm (n=34) and XY (n=32) littermate controls were fed for 16, 20, 24 or 28 weeks on either diet 1 (comprising: 42% butterfat and 0.1% cholesterol), or diet 2 (comprising 42% butterfat, 1.25% cholesterol and 0.5% cholate) to promote lesion formation. Mice were then sacrificed, the hearts perfused with saline and frozen at -80degC. Five, 8 micrometre transverse cryosections were taken at approximately 100 micrometre intervals through the aortic root of each heart. Sections were stained with oil red O and counterstained with haematoxylin, photographed, and lipid-stained areas quantified via digital analysis, and expressed as percentage of lumen area.

Results: Negligible lipid deposition was observed in mice fed on diet 1. Lipid deposition in Tfm and XY littermates fed on diet 2 was: 2.59 (1.02) versus 1.11 (0.22) % at 16 weeks (p=0.17), 0.79 (0.20) versus 1.10 (0.17) % at 20 weeks (p=0.25), 0.52 (0.06) versus 0.77 (0.25) % at 24 weeks (p= 0.12) and 3.74 (0.72) versus 0.31 (0.11) % at 28 weeks (p=0.00003) respectively. Similarly, change in body weight of Tfm and XY littermates fed on diet 2 was: 11.1 (1.91) versus 3.94 (0.54) g at 16 weeks (p=0.001), 15.8 (2.26) versus 4.67 (1.20) g at 20 weeks (p=0.0002), 21.3 (3.10) versus 6.13 (1.82) g at 24 weeks (p= 0.0009) and 20.5 (4.09) versus 4.25 (1.65) g at 28 weeks (p=0.01) respectively.

Conclusion: Low endogenous testosterone and an inactive AR in the Tfm mouse is associated with increased lipid burden within the aortic root following feeding for 28 weeks on a cholesterol-enriched diet.