| Male gender is one of the classic risk factors for coronary artery disease (CAD), and androgens have traditionally been regarded as the proximate cause underlying this male disadvantage. However, studies over recent years that men with CAD have lower serum testosterone(T) levels compared with control and T levels correlate positively with high density lipoprotein(HDL) concentration in men have challenged the notion. It has been a focus that whether it is beneficial or deteriorative for men supplement with androgen. In this study we try to explore the roles of T in male cardiovascular diseases by examine the effects of T on the lipoprotein metabolism, on the secretion of vascularactive substance in endothelial cells and the expression of endothelium-related gene.Objectives: (1) To explore the impact of T on metabolism of lipoprotein in castrated male rabbits fed a cholesterol-rich diet;(2)To determine the effect of T on the secretion of adrenomedullin(ADM) and endothlin-1(ET-1) in cultured endothelial cells;(3)To detecte the change of expression of thrombomodulin(TM), endothelial lipase (EL) and androgen receptor(AR) under the presence of T in cultured medium.Materials and methods:(1)Experiment one Forty male rabbits were randomized into six groups(n=7 per group), (1)castraed group fed a standard diet, (2)sham group fed a cholesterol-rich diet, (3)castraed group fed a cholesterol-rich diet and placebo, (4)castrated group fed a cholesterol-rich diet and low dosage T(3mg/kg), (5)castrated group fed a cholesterol-rich diet and physiological dosage T(6mg/kg), (6)castrated group fed a cholesterol-rich diet and supraphysiological dosage T(12mg/kg).The following parameters in circulating blood were examined before castration, 2w after castration and 4 months after castration: total T, estradiol, high density lipoprotein(HDL), low density lipoprotein(LDL), total cholesterol(TC), triglycerol(TG), lipoprotein a(Lp(a)), apoprotein A- I (apoA-1), apoB, hepatic lipase(HL), lipoprotein lipase(LPL),and the following ratio were caculated: E2/TT (%)> TC/HDL, LDL/apoB, apoB/apoA- I, LPL/HL. (2)Experiment two The culturedendothelial cells were divided into Severn groups (1)contro group, (2)T group(2, 10, 50, 100mg/L), (3)LDL group(50 , 100mg/L), (4)OX-LDL group(50 , 100mg/L), (5)LDL(50mg/L)+OX-LDL group(50mg/L), (6)T(2> 10, 50mg/L)+OX-LDL group(50mg/L), (7)T(10mg/L)+LDL(50mg/L)+OX-LDL(50mg/L) group. The supernatant were collected after 24hr incubation and ADM and ET-1 were determined in supernatant.(3)Experiment three Cultured endothelial cells incubated with T(0, 2, 6, 10, 20, 50, 100, 500, 1000mg/L) for 24hr and western bloting was carried out to detect the effect of T on the expression of TM in cultured endothelial cells.Northern bloting was also carried out to determined the expression of TM, EL, AR mRNA in cultured endothelial cells at T concentration of 0,2 > 10, 50, 100mg/Landattime4, 8, 12, 24hr of 10mg/L.Results: (1)Experiment one The change of sex hormone levels and lipase TT and E2 levels decreased apparently after castration compared with control group(p<0.01,respectively), but the ratio of E2/TT (%) elevated(w before castration,p<0.01). The activity of HL and LPL were lower after castration (vs before castration, p<0.01), LPL/HL did not changed significantly(v5 before castration, p>0.05). 4 months after T supplement, the TT levels rised and the levels in supraphysiological dosage was highest, the levels of E2 exhibits the similar trend to the TT, the ratio of E2/TT was highest in castrated group. The activity of HL and LPL were increased in T supplement groups and exited no significantly difference between the physiological group and sham operation group. The levels of lipid and lipoproteins The levels of TG, TC, HDL, LDL, LPa, apoB, apoB/apoA-I elevated, apoA-1, LDL/apoB decreased, TC/HDL did not change significantly 2w after castration. 4 months after castration, the levels of TC, LDL, HDL in castrated group fed a cholesterol-rich diet were significantly higher than group fed a standard diet(p<0.05), the change of...
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