Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone that is secreted primarily by the adrenal gland and is the most abundant sex steroid. Although the mechanisms of action of exogenously administered DHEA have not been fully illuminated, they may result in both direct and indirect physiologic effects. Direct effects include GABA-a receptor complex and NMDA receptor modulation and enhanced pancreatic beta cell insulin secretion and anti-glucocorticoid activities.

DHEA是一种有效的抗凋亡因子，能逆转血清剥夺所引起的前列腺癌细胞(DU145和LNCaP细胞系)和结肠癌细胞(Caco2细胞系)的凋亡。通过APOPercentage测定和流式细胞术(FACS)分析DU145细胞显示（凋亡从0.587±0.053减少到12小时DHEA或NGF处理后的0.142±0.0016或0.059±0.002；n=3，P<0.01），DHEA显著减少这三种癌症细胞类型的血清剥夺诱导的凋亡。DHEA的抗凋亡效应是剂量依赖性的，EC50在纳摩尔浓度范围内（EC50：DU145细胞中为11.2±3.6 nM，Caco2细胞中为12.4±2.2 nM）[1]。DHEA是人体主要的性类固醇前体，可以直接转化为雄激素。通过掺入Oxytetracycline核苷酸测定评估，DHEA（≥1 μM）以剂量依赖的方式抑制Chub-S7细胞增殖。DHEA处理以剂量依赖的方式抑制分化前脂肪细胞中关键糖皮质激素调节基因H6PDH（≥100 nM）和HSD11B1（≥1 μM）的表达。DHEA处理（≥1 μM）诱导11β-HSD1氧化还原酶活性显著降低（≥1 μM）。在最高DHEA剂量（25 μM DHEA）使用下分化脂肪细胞中脱氢酶活性增加[2]。

在雄性B6小鼠饮食中添加DHEA（0.45% w/w），并持续治疗8周。与食用对照AIN-76A饮食的小鼠相比，小鼠体温降低。进一步比较显示，对照组小鼠和按需喂养小鼠之间也存在显著差异。摄入DHEA的动物在29次测试中有26次显示出比食用对照饮食的小鼠体温显著降低；与DHEA饮食量相同的按需喂养小鼠受影响较小。在29次测试中仅8次体温显著低于自由采食AIN-76A饮食的小鼠。在29次测试中有21次，摄入DHEA或与DHEA按需喂养的小鼠的体温显著不同。食用对照饮食的小鼠体重显著大于食用DHEA饮食或与DHEA按需喂养的小鼠。DHEA喂养小鼠的食物摄入量显著减少。DHEA通过食物限制及其他独立机制降低体温[3]。

Chub-S7 cells are incubated in DMEM containing cold DHEA (20 nM) and tritiated DHEA (0.2 μCi/well) for 48 h. Following incubation, steroids are extracted using dichloromethane separated by thin-layer chromatography using n-hexane/1-hexanol (75:25) as the mobile phase system. Metabolites are identified by comigration with unlabeled reference steroids that are visualized by exposure to Lieberman-Burchard reagent (ethanol-acetic anhydride-sulfuric acid). Steroid conversion is quantified using a LabLogic AR-200 scanner. Protein concentration is measured using a colorimetric 96-well plate assay and used to normalize conversion. Activity is expressed as percent conversion[2].

DHEA is dissolved in DMSO and stored, and then diluted with appropriate medium before use[2]. Chub-S7 preadipocytes and human primary preadipocytes are seeded into a 24-well plate at densities 1×105 and 2.5×105 respectively. Following overnight culture, medium is supplemented with DHEA, androstenediol, or DHEAS (0-100 μM). Following 24-, 48-, or 72 h incubation, cell proliferation is assessed by incubation with radiolabeled thymidine (0.2 μCi/well) for the final 6 h of culture. Proteins are precipitated with TCA, and cells are scraped in NaOH. The respective content of radiolabeled nuclear material in the resulting lysates is analyzed by scintillation counting. Data are expressed as percentage of control[2].

Mice are fed Purina Lab Chow until the start of experiments (Day 0). Groups of five mice are then fed pelleted AIN-76A diet containing either no additive or DHEA (0.45% w/w) between 0900 and 1000 hr. Diets are stored at 4°C for no longer than six months to maintain optimal activity. Mice are given the diets ad libitum, except for mice that are pair-fed to mice treated with DHEA. The amounts of AIN-76A diet the pair-fed mice received are determined by the weight of food consumed by the DHEA-fed mice on a daily basis. Body weights (grams) are measured at different time points starting at Day 1 and ending at Day 59. Daily food intakes (grams per day) are determined by weighing the food consumed per cage of five mice. The mean±SEM values are calculated for weeks 1 to 8 (n=7); week 9 had only 3 days.