Sholl S A, Pomerantz S M
Endocrinology. 1986 Oct;119(4):1625-31. doi: 10.1210/endo-119-4-1625.
The present study characterizes putative androgen receptor activity in the cerebral cortex cytosol of the female fetal monkey (Macaca mulatta) on days 125-135 postconception. Binding activities were compared using tritiated 5 alpha-dihydrotestosterone (DHT) and methyltrienolone (R1881) as ligands. Receptor concentration and association constants (Ka) were estimated from bound/total vs. total ligand binding curves. For R1881 and DHT, Ka values were 4.3 X 10(9) and 7.0 X 10(9) M-1, respectively. Receptor concentrations using the two ligands were estimated to be 5.5 X 10(-15) mol/mg protein (R1881; n = 2) and 1.7 X 10(-15) mol/mg protein (DHT). Analysis of receptor binding on DEAE-cellulose columns (KCl gradient) revealed multiple binding peaks (0.05-0.3 M KCl); similar elution profiles were obtained for the two ligands. Competition with either R1881 or DHT significantly reduced [3H]DHT binding throughout the KCl gradient, while triamcinolone acetonide had no effect. In contrast, [3H]R1881 binding was reduced by all three competitors. Cytosol from fetal male seminal vesicles had [3H]ligand-binding activity that was chromatographically similar to that of cerebral cortex. In contrast, binding in fetal male serum was negligible. Competition of cerebral cortex binding with a variety of hormones, including SCH-16423, progesterone, and cortisol, and analysis of the results on DEAE-cellulose suggested that there may be additional species of ligand-binding molecules. In summary, the findings verify the existence of a specific androgen receptor(s) in the cerebral cortex of fetal female rhesus monkeys. Its presence may be important for understanding both the influence of androgens on central nervous system development and the potential for teratogenic agents to disrupt normal patterns of central nervous system development.
本研究对受孕后125 - 135天雌性胎猴（恒河猴）大脑皮质胞质溶胶中假定的雄激素受体活性进行了表征。使用氚标记的5α - 双氢睾酮（DHT）和甲基三烯olone（R1881）作为配体比较结合活性。从结合/总配体与总配体结合曲线估计受体浓度和缔合常数（Ka）。对于R1881和DHT，Ka值分别为4.3×10⁹和7.0×10⁹ M⁻¹。使用这两种配体估计的受体浓度分别为5.5×10⁻¹⁵ mol/mg蛋白质（R1881；n = 2）和1.7×10⁻¹⁵ mol/mg蛋白质（DHT）。对DEAE - 纤维素柱上的受体结合（KCl梯度）分析揭示了多个结合峰（0.05 - 0.3 M KCl）；两种配体获得了相似的洗脱图谱。用R1881或DHT竞争在整个KCl梯度中均显著降低[³H]DHT结合，而曲安奈德则无影响。相比之下，[³H]R1881结合被所有三种竞争者降低。来自雄性胎猴精囊的胞质溶胶具有[³H]配体结合活性，其色谱行为与大脑皮质相似。相比之下，雄性胎猴血清中的结合可忽略不计。用包括SCH - 16423、孕酮和皮质醇在内的多种激素竞争大脑皮质结合，并在DEAE - 纤维素上分析结果表明可能存在其他种类的配体结合分子。总之，这些发现证实了雌性胎恒河猴大脑皮质中存在特异性雄激素受体。其存在对于理解雄激素对中枢神经系统发育的影响以及致畸剂破坏中枢神经系统正常发育模式的可能性可能很重要。
