Wright B E, Porter J R, Browne E S, Svec F
Department of Physiology, Louisiana State University Medical Center, New Orleans 70119.
Int J Obes Relat Metab Disord. 1992 Aug;16(8):579-83.
Dehydroepiandrosterone (DHEA) reduces weight gain in the hypercorticosteronemic Zucker fatty rat, an animal model of genetic obesity. However, the mechanism of action of DHEA is still unclear. We propose that DHEA acts as an antiglucocorticoid in the Zucker fatty rat. To test this hypothesis we examined DHEA's ability to block the activation of the glucocorticoid-inducible enzymes tyrosine aminotransferase (TAT) and ornithine decarboxylase (ODC) by dexamethasone (i.p. 5 micrograms/100 g body weight) in hepatic tissue of 6-10 week old Zucker rats. Injections of DMSO, the vehicle, served as a control. DHEA alone did not affect TAT, but when DHEA (500 micrograms/100 g b.w.) was administered simultaneously with dexamethasone, activation did not occur. Similar results were seen using a second tissue (kidney). We conclude that DHEA can act acutely as an antiglucocorticoid in the young obese Zucker rat and hypothesize that its chronic anti-obesity effect may reflect, at least in part, a chronic antiglucocorticoid activity.
脱氢表雄酮（DHEA）可减少高皮质酮血症Zucker肥胖大鼠（一种遗传性肥胖动物模型）的体重增加。然而，DHEA的作用机制仍不清楚。我们提出DHEA在Zucker肥胖大鼠中作为一种抗糖皮质激素发挥作用。为了验证这一假设，我们检测了DHEA在6 - 10周龄Zucker大鼠肝组织中阻断地塞米松（腹腔注射5微克/100克体重）诱导的糖皮质激素诱导酶酪氨酸转氨酶（TAT）和鸟氨酸脱羧酶（ODC）激活的能力。注射二甲基亚砜（DMSO，溶剂）作为对照。单独使用DHEA对TAT没有影响，但当DHEA（500微克/100克体重）与地塞米松同时给药时，未发生激活。在第二种组织（肾脏）中也观察到了类似结果。我们得出结论，DHEA在年轻肥胖的Zucker大鼠中可作为一种急性抗糖皮质激素发挥作用，并推测其慢性抗肥胖作用可能至少部分反映了一种慢性抗糖皮质激素活性。
