Effects Of Exogenous Testosterone On Serum Lipids And Atherosclerosis In Castrated Rabbits

ObjectiveThe effect of androgens on serum lipids, lipoproteins, apolipoproteins and atherosclerosis is controversial. We therefore studied the effect of serum testosterone level on serum lipids, lipoproteins, apolipoproteins and experimental atherosclerosis prospectively in castrated rabbits.MethodsIn the first part, thirty-six male New Zealand White rabbits were randomized into bilateral castration group (n=27) and sham operation group (n=9), and then the castrated rabbits were randomized into hypotestosteronemia group, physitestosteronemia group and hypertestosteronemia group. From 5th week till 13th week after castration, the three groups of castrated rabbits were intramuscularly injected testosterone undecanoate 3mg/kg, 6mg/kg, and 6mg/kg once every two weeks respectively, whereas the sham-operated rabbits did not receive any testosterone. All animals were fed a standard diet without cholesterol during the 8-week treatment period.In the second part, forty-five male New Zealand White rabbits were randomized into bilateral castration group (n=36), and sham operation group (n=9), and then the castrated rabbits were randomized to hypotestosteronemia group, physitestosteronemia group, hypertestosteronemia group and placebo group. The first three groups of castrated rabbits were intramuscularly injected testosterone undecanoate 3mg/kg, 6mg/kg, and 12mg/kg once every two weeks respectively since the operation, whereas the placebo group and the sham-operated rabbits did not receive any testosterone. All animals were fed a cholesterol-rich diet during the 16-week treatment period.Blood samples were collected for determination of serum levels of total testosterone (TT), estradiol (E2), lipids, lipoproteins and apolipoproteins at the 1st week before treatment in both part rabbits and 8th weeks after injection in the first part rabbits, 16th weeks in the second part rabbits. At the end of the study (week 16), the aortic of the second part rabbits was analyzed morphmetrically and immunohistologically and the aortic cholesterol content were determined chemically.ResultsAfter castration of the first and the second part rabbits, the serum level of TT decreased significantly to the lowest level, and increased depending on doses of TU supplement. The severe endogenous hypoteststeronemia exogenous hypoteststeronemia, physitestosteronemia and hypertestosteronemia models in castrated rabbits were successfully made in this study. Both in the first and second part of rabbits, average serum lipids, atherogenic lipoproteins and apolipoproteins, such as total of cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), etc.were significantly higher in the placebo group, exogenous hypoteststeronemia and hypertestosteronemia groups than those in the sham operated group and the exogenous hysitestosteronemia group. Atherosclerosis, as evaluated by the cholesterol content (mmol/g) and intimal thickening in the proximal aortic arch, were also severer in the placebo group, exogenous hypoteststeronemia and hypertestosteronemia groups than in the sham-operated group and the exogenous hysitestosteronemia group.ConclusionExogenous testosterone, at physiological level seems have a good effect on the serum lipids, lipoproteins, lipoproteins and atherosclerosis in castrated male rabbits, whereas the endogenous or enexogenous hypotestosteronemia and hypertestosteronemia may have not.