Background-Recent studies have suggested that testosterone has a protective effect in the arterial vascular system. However, little is known about the molecular aspects of the mechanism(s) involved in these processes. The aim of the present study was to investigate the effect of testosterone on neointimal plaque development and on the expression of the vascular androgen receptor. Methods and Results-Neointimal plaque formation was induced by endothelial denudation in the aortas of male New Zealand White rabbits. Aortic ring segments were cultured for 21 days after endothelial denudation. Testosterone was applied to the culture medium in different doses. Compared with the non-hormone-treated control group, a significant inhibition of neointimal plaque development (expressed as the intima/media ratio) was found at testosterone concentrations of 10 ng/mL (Pϭ0.037) and 100 ng/mL (Pϭ0.012; intima/media ratios: median of controls, 0.25; median of 10 ng/mL testosterone group, 0.15; median of 100 ng/mL testosterone group, 0.16). Associated with this inhibitory effect on plaque size was a 50% increase of the amount of androgen receptor mRNA in the arterial segments treated with testosterone. Conclusion-The beneficial effects of testosterone on postinjury plaque development underlines, at least in males, the important role of androgens in the vascular system. As our data suggest, the vascular androgen receptor is probably involved in these processes. Further studies are required to characterize the androgen receptor-dependent pathways in the vascular system. Key Words: testosterone Ⅲ receptors, androgen Ⅲ atherosclerosis T he role of androgens in atherogenesis is controversial 1 ; however, in recent years, several authors have found a number of beneficial effects of testosterone, at least in men. Animal studies have documented an inhibitory effect on plaque development in the cholesterol-fed rabbit model, 2,3 whereas in recent clinical investigations, acute hemodynamic effects of testosterone on coronary vasomotion and stress-test induced ischemia were observed. 4,5 Thus far, only limited information is available regarding the possible involvement of arterial androgen receptors in these processes. Thus, the aim of the present study was to investigate, in an experimental model, (1) the dose-dependent effects of testosterone on plaque development, (2) the expression of the androgen receptor in arteries, and (3) possible dose-dependent changes of androgen receptor expression induced by testosterone. Methods Organ Culture SystemTwelve-week-old male New Zealand White rabbits were used for the present study. The rabbits received standard chow without cholesterol (Altromin Inc) and were housed individually (no female rabbits were present). After sacrifice, the abdomen was opened under sterile conditions, and the connective tissue was removed from the aorta. A 3F-Fogarty catheter (Baxter Inc) was inserted below the iliac bifurcation, and endothelial denudation was performed once with the inflated catheter. The aorta was then comp...

Catheter transmitted endovascular irradiation with the liquid beta-emitter Rhenium-188 after vascular injury is feasible and effectively reduced neointimal hyperplasia in hypercholesterolemic rabbits. A significant reduction of the neointimal formation could be found already at a radiation absorbed dose of 15 Gy at the vessel surface. Following a surface dosage of 45 Gy the proliferative response to the vessel injury is almost completely abolished.

Large epidemiological studies have proved that the risk of coronary heart disease in postmenopausal women can be decreased by oestrogen replacement therapy. The effect is triggered by metabolic processes in the liver (decrease of LDL-cholesterol, increase of HDL-cholesterol) as well as by direct impact on the arterial wall (anti-oxidation, relaxation, anti-proliferation). The therapeutical usage of oestrogens is limited by an increased incidence of breast and endometrial cancer. Cyclic application of progestogens virtually eliminates the risk. Unfortunately, progestogens may antagonise the atheroprotective effect of oestrogens. Structurally modified oestrogens as well as selective oestrogen receptor modulators were investigated in clinical trials. They might provide the desired atheroprotective effects of oestrogen without negative side effects on the mammary gland or the endometrium. In this respect isoflavones also known as phytoestrogens, were analysed. They are widespread and occur naturally in many plants, especially in soy products. Cell culture and animal experiments as well as clinical studies revealed that phytoestrogens such as genistein and daidzein act atheroprotectively in the same way as oestrogen. Effects on the mammary gland or the endometrium could not be detected, but positive side effects on the bone metabolism and the decrease of certain types of cancer could be observed. In total, the therapeutical application of phytoestrogens in postmenopausal women seems to be of real and great benefit. We conclude that in women the risk of death from coronary heart disease increases after the onset of menopause. Recently discovered properties of phyto-oestrogens seem to be of great benefit as they do not seem to have any side effects on the mammary gland and the endometrium which are limiting factors for oestrogen replacement therapy.

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