Rifka S M, Cutler G B, Sauer M A, Loriaux D L
Endocrinology. 1978 Oct;103(4):1103-10. doi: 10.1210/endo-103-4-1103.
Many previous studies have demonstrated effects of gonadal steroids on adrenal weight in the rat. Most of these effects are indirect, depending upon alterations in the pituitary-adrenal axis for their expression. In this study we have attempted to examine the direct effects of gonadal steroids on adrenal weight in the rat. This was done using hypophysectomized, castrated male rats receiving ACTH replacement, a model which excludes pituitary-adrenal feedback effects. Estradiol-treated rats did not differ from controls, whereas testosterone-treated rats exhibited a small but statistically significant decrease in adrenal weight. As a first step in exploring the mechanism of this androgen effect, we have identified a specific dihydrotestosterone-binding protein in the rat adrenal gland. A single class of high affinity (Kd = 0.6-2.0 x 10(-8) M), saturable (28 fmol/mg cytosol protein), cytoplasmic binding sites was found using both protamine sulfate precipitation and dextran-coated charcoal assays. The specificity, sedimentation coefficient on sucrose gradient, and sensitivity to sulfhydryl reagents and heat of this dihydrotestosterone-binding protein are typical of the cytoplasmic androgen receptor from other androgen target tissues such as prostrate. We conclude that testosterone can decrease rat adrenal weight directly, and that the mechanism may involve a high affinity binding protein, as has been shown in other androgen-responsive systems.
许多先前的研究已经证明性腺类固醇对大鼠肾上腺重量的影响。这些影响大多是间接的，其表现依赖于垂体-肾上腺轴的改变。在本研究中，我们试图研究性腺类固醇对大鼠肾上腺重量的直接影响。这是通过对接受促肾上腺皮质激素替代治疗的垂体切除、去势雄性大鼠进行实验来完成的，该模型排除了垂体-肾上腺的反馈作用。接受雌二醇治疗的大鼠与对照组没有差异，而接受睾酮治疗的大鼠肾上腺重量出现了虽小但具有统计学意义的下降。作为探索这种雄激素作用机制的第一步，我们在大鼠肾上腺中鉴定出一种特异性的双氢睾酮结合蛋白。使用硫酸鱼精蛋白沉淀法和葡聚糖包被活性炭分析法均发现了一类单一的高亲和力（解离常数Kd = 0.6 - 2.0×10⁻⁸M）、可饱和（28飞摩尔/毫克胞浆蛋白）的胞质结合位点。这种双氢睾酮结合蛋白的特异性、在蔗糖梯度上的沉降系数以及对巯基试剂和热的敏感性，与来自其他雄激素靶组织如前列腺的胞质雄激素受体的典型特征一致。我们得出结论，睾酮可直接降低大鼠肾上腺重量，其机制可能涉及一种高亲和力结合蛋白，正如在其他雄激素反应系统中所显示的那样。
