Endocrine Abstracts (2006) 11 P403

Low endogenous testosterone induces fatty streak formation following cholesterol feeding in the testosterone deficient testicular feminised mouse and castrated male

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.


Low endogenous testosterone is associated with atherosclerosis in elderly men. The aim of this study was to examine the role of the androgen receptor (AR) in the development of atherosclerosis and determine whether an inactive AR coupled with testosterone deficiency, inherent to the testicular feminised (Tfm) mouse, is associated with atherosclerosis following cholesterol feeding compared to surgically-castrated male littermates with AR intact.

Ten-week-old Tfm mice and XY controls littermates were separated into 4 groups and fed a cholesterol-enriched diet (comprising 42%butterfat, 1.25%cholesterol and 0.5%cholate) for a period of 28-weeks. Group 1, Tfm mice fed diet alone (n=4), Group 2, XY controls fed diet alone (n=4), Group 3, Sham-operated Tfm mice (n=6) and Group 4, castrated XY controls (n=6). Mice were sacrificed, the hearts perfused with saline and frozen at −80°C. Five, 8 micrometre 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, and lipid-stained areas quantified via digital analysis, and expressed as percentage of medial area.

Table 1
AR/Testosterone StatusLipid Deposition (% medial area)
TfmAR deficient/low testosterone3.74 (0.72)
XYAR intact/physiological testosterone0.31 (0.11)*
Tfm – shamAR deficient/low testosterone2.15 (0.61)
XY – castrateAR intact/low testosterone4.96 (0.49)*
P<0.01 versus respective control

Low endogenous testosterone is associated with increased fatty streak formation in testosterone deficient Tfm mice with an inactive AR and AR intact castrated XY littermates compared to controls following feeding for 28 weeks on a cholesterol-enriched diet.

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