Naess O, Haug E, Attramadal A, Aakvaag A, Hansson V, French F
Endocrinology. 1976 Nov;99(5):1295-303. doi: 10.1210/endo-99-5-1295.
The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of androgen "insensitive" (Tfm) rats possess androgen receptors. However, in the Tfm rats the androgen binding per mg protein was only 10-15% of that in the corresponding normal littermates (Nl). The physicochemical properties of the androgen receptors in the anterior pituitary of the Tfm rat were indistinguishable from those of the normal rat. Thus, no distinctive differences were observed with regard to electrophoretic mobility in 3.25% polyacrylamide gels, isoelectric point (pI=5.8), binding affinity (KD=1.5 X 10(-9)M), temperature stability, sulfhydryl dependence and steroid specificity. It is, therefore, likely that the very low androgen binding capacity by the anterior pituitary and the central nervous system is due to an extreme reduction in the receptor number rather than to the presence of abnormal receptors. Since in the Tfm animals the androgen receptor number is reduced by 85-90%, it is to be expected that very high doses of androgens would be required to achieve hormonal effects. In fact, low doses of 5alpha-dihydrotestosterone propionate (50 mug/100 g body weight) given sc daily for 12 days had no effect on serum levels of LH and FSH. However, very high doses (2 mg/100 g body weight) of testosterone propionate and 5alpha-dihydrotestosterone propionate, which maintained circulating androgen levels above 20 ng/ml, significantly reduced serum gonadotropin levels in castrated Tfm rats. In normal littermates both low and high doses of the androgens suppressed gonadotropin secretion to low levels. These findings strongly indicate that androgen receptors are essential to androgen action on the anterior pituitary and central nervous system in the rat. The serum levels of testosterone (7.7+/-0.15 (SE) ng/ml) and 5alpha-dihydrotestosterone (0.37+/-0.06 ng/ml) were significantly higher in intact Tfm rats than in normal littermates (2.6+/-0.03 and less than 0.1 ng/ml, respectively). The failure of the elevated concentrations of serum androgens to reduce the high serum levels of LH and FSH in intact Tfm rats is most likely due to the extreme reduction of the androgen receptor number and the consequent insufficient hypothalamic and/or pituitary response to androgens.
雄激素“不敏感”（Tfm）大鼠的垂体前叶、下丘脑、视前区和大脑皮层的胞质溶胶部分含有雄激素受体。然而，在Tfm大鼠中，每毫克蛋白质的雄激素结合量仅为相应正常同窝仔鼠（Nl）的10 - 15%。Tfm大鼠垂体前叶中雄激素受体的物理化学性质与正常大鼠的无异。因此，在3.25%聚丙烯酰胺凝胶中的电泳迁移率、等电点（pI = 5.8）、结合亲和力（KD = 1.5×10⁻⁹M）、温度稳定性、巯基依赖性和类固醇特异性方面均未观察到明显差异。所以，垂体前叶和中枢神经系统的雄激素结合能力极低很可能是由于受体数量极度减少，而非存在异常受体。由于在Tfm动物中雄激素受体数量减少了85 - 90%，预计需要非常高剂量的雄激素才能产生激素效应。事实上，每天皮下注射低剂量的丙酸5α - 双氢睾酮（50微克/100克体重），持续12天，对血清促黄体生成素（LH）和促卵泡生成素（FSH）水平没有影响。然而，非常高剂量（2毫克/100克体重）的丙酸睾酮和丙酸5α - 双氢睾酮，可使循环雄激素水平维持在20纳克/毫升以上，能显著降低去势Tfm大鼠的血清促性腺激素水平。在正常同窝仔鼠中，低剂量和高剂量的雄激素均能将促性腺激素分泌抑制到低水平。这些发现有力地表明，雄激素受体对于大鼠垂体前叶和中枢神经系统的雄激素作用至关重要。完整Tfm大鼠的血清睾酮水平（7.7±0.15（SE）纳克/毫升）和5α - 双氢睾酮水平（0.37±0.06纳克/毫升）显著高于正常同窝仔鼠（分别为2.6±0.03和低于0.1纳克/毫升）。完整Tfm大鼠血清雄激素浓度升高却未能降低血清LH和FSH的高水平，很可能是由于雄激素受体数量极度减少，以及随之而来的下丘脑和/或垂体对雄激素的反应不足。
