Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom.
Research Institute of the McGill University Health Centre (RI-MUHC), McGill University, Montréal, Québec, Canada.
Can J Cardiol. 2022 Dec;38(12):1854-1864. doi: 10.1016/j.cjca.2022.09.018. Epub 2022 Sep 22.
Androgens, including testosterone and its more potent metabolite dihydrotestosterone, exert multiple actions in the body. Physiologically, they play a critical role in male sex development. In addition, they influence vascular function, including arterial vasodilation and mediation of myogenic tone. Androgens are produced from 9 weeks' gestation in the human fetal testis, as well as in small amounts by the adrenal glands. Serum concentrations vary according to age and sex. The vasculature is a target for direct actions of androgens, which bind to various sex hormone receptors expressed in endothelial and vascular smooth muscle cells. Androgens exert both vasoprotective and vasoinjurious effects, depending on multiple factors including sex-specific effects of androgens, heterogeneity of the vascular endothelium, differential expression of androgen and sex hormone receptors in endothelial and vascular smooth muscle cells, and the chronicity of androgen administration. Long-term administration of androgens induces vasoconstriction and influences endothelial permeability, whereas acute administration may have opposite effects. At the cellular level, androgens stimulate endothelial cell production of nitric oxide and inhibit proinflammatory signalling pathways, inducing vasorelaxation and vasoprotection. However, androgens also activate endothelial production of vasoconstrictors and stimulate recruitment of endothelial progenitor cells. In humans, both androgen deficiency and androgen excess are associated with increased cardiovascular morbidity and mortality. This review discusses how androgens modulate vascular sex differences across the lifespan by considering the actions and production of androgens in both sexes and describes how cardiovascular risk is altered as levels of androgens change with aging.
雄激素，包括睾酮及其更有效的代谢产物二氢睾酮，在体内发挥多种作用。从生理上讲，它们在男性性发育中起着关键作用。此外，它们还影响血管功能，包括动脉血管舒张和肌源性张力的调节。雄激素在人类胎儿睾丸中从第 9 周妊娠开始产生，也少量由肾上腺产生。血清浓度随年龄和性别而变化。血管是雄激素直接作用的靶标，雄激素与内皮细胞和血管平滑肌细胞中表达的各种性激素受体结合。雄激素具有血管保护和血管损伤作用，这取决于多种因素，包括雄激素的性别特异性作用、血管内皮的异质性、内皮细胞和血管平滑肌细胞中雄激素和性激素受体的差异表达，以及雄激素给药的慢性。长期雄激素给药可诱导血管收缩并影响内皮通透性，而急性给药可能具有相反的作用。在细胞水平上，雄激素刺激内皮细胞产生一氧化氮并抑制促炎信号通路，诱导血管舒张和血管保护。然而，雄激素也激活内皮细胞产生血管收缩剂并刺激内皮祖细胞的募集。在人类中，雄激素缺乏和雄激素过多都与心血管发病率和死亡率的增加有关。本综述通过考虑两性中雄激素的作用和产生，讨论了雄激素如何在整个生命周期中调节血管性别差异，并描述了随着年龄的增长，雄激素水平的变化如何改变心血管风险。
