Department of Biomedical Sciences, University of Missouri, Columbia, MO, 65211, USA.
Biol Sex Differ. 2012 May 23;3(1):10. doi: 10.1186/2042-6410-3-10.
Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.
Pigs received intracoronary infusions of physiologic levels (1-100 nM) of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1-100 nM) of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.
In vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.
Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.
低内源性睾丸激素水平已被证明是心血管疾病发展的一个风险因素，并且提倡用睾丸激素替代疗法来获得心血管益处；然而，内源性睾丸激素水平对雄激素给药后急性冠状动脉血管舒缩反应的影响尚不清楚。本研究的目的是比较急性雄激素给药对完整和去势雄性猪体内冠状动脉传导和体外冠状动脉微血管直径的影响。
猪接受了生理水平（1-100 nM）的睾丸激素、代谢物 5α-二氢睾丸酮和差向异构体表睾酮的冠状动脉内输注，同时连续监测左前降支冠状动脉血流量和平均动脉压。处死猪后，分离、插管并暴露于生理浓度（1-100 nM）的睾丸激素、5α-二氢睾丸酮和表睾酮下，评价雄激素受体对急性雄激素扩张反应的影响，对导管和阻力冠状动脉进行雄激素受体的实时 PCR 和免疫组织化学检测。
在体内，与去势雄性相比，完整雄性中睾丸激素和 5α-二氢睾丸酮引起的冠状动脉传导增加更大。在体外，完整雄性中，睾丸激素和 5α-二氢睾丸酮引起的微血管最大扩张百分比与去势雄性相似。在这两项研究中，表睾酮在完整雄性中均能使传导和微血管直径从基线显著增加。完整和去势雄性的雄激素受体 mRNA 表达和免疫组织化学染色相似。
外源性雄激素给药后的急性冠状动脉血管反应增加了内源性睾丸激素，这种作用与雄激素受体表达的变化无关。
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