Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
J Sex Med. 2011 Nov;8(11):2960-82; quiz 2983. doi: 10.1111/j.1743-6109.2011.02523.x.
The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions.
The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging.
We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions.
Data reported in the literature were analyzed, reviewed, and discussed.
DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7β DHEA, and 7α and 7β epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women.
DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be associated with a host of pathologies; however, the clinical efficacy of DHEA supplementation in ameliorating patho-physiological symptoms remains to be evaluated.
大量脱氢表雄酮（DHEA）及其硫酸化衍生物（DHEA-S）的循环表明其在人体生理学中具有生理作用。在中枢神经系统中，DHEA 被认为是一种具有广泛功能的神经甾体。
本综述的目的是讨论 DHEA 的代谢、生化和生理作用机制，以及 DHEA 在衰老和改善与衰老相关的多种病理状况中的潜在作用。
我们检查了来自各种研究的文献中报道的关于 DHEA 在正常和病理条件下的作用的临床前和临床数据。
分析、审查和讨论文献中报道的数据。
DHEA 通过涉及特定膜受体的多种信号通路及其转化为雄激素和雌激素衍生物（如雄激素、雌激素、7α 和 7β DHEA 以及 7α 和 7β 表雄酮衍生物）发挥作用，这些衍生物通过其特定受体发挥作用。这些途径包括：一氧化氮合酶的激活、γ-氨基丁酸受体的调节、N-甲基-D-天冬氨酸、sigma 受体（Sigma-1）、炎症因子、黏附分子和活性氧的差异表达等。临床和流行病学研究表明，DHEA 水平较低可能与缺血性心脏病、内皮功能障碍、动脉粥样硬化、骨质流失、炎症性疾病和性功能障碍有关。最重要的是，在对男性和女性进行的 DHEA 临床研究中，没有报告 DHEA 出现显著的不良反应或副作用。
DHEA 可调节内皮功能，减轻炎症，改善胰岛素敏感性、血流、细胞免疫、身体成分、骨代谢、性功能和虚弱时的体力，并提供神经保护、改善认知功能和增强记忆力。DHEA 具有多种作用，DHEA 和 DHEA-S 水平降低可能与多种疾病有关；然而，DHEA 补充剂改善病理生理症状的临床疗效仍有待评估。
