Michael R P, Bonsall R W
Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia 30322.
J Clin Endocrinol Metab. 1990 Oct;71(4):868-74. doi: 10.1210/jcem-71-4-868.
To examine the possible sites of action of the synthetic estrogen diethylstilbestrol (DES) in the developing primate, [3H]DES (250 mu Ci, iv, or 500 mu Ci, sc) was administered directly into two rhesus and nine cynomolgus macaque fetuses at about 122 days gestation (range, 121-124 days). The location of cells accumulating radioactivity 60 min later was examined by autoradiography in two males and two females. In females, labeled neurons were observed in the hypothalamus, preoptic area, and amygdala, but not in the cerebral cortex. In one male a similar pattern of uptake was observed, but percentages of labeled neurons were lower, and in the other male very little labeling was observed in any region. The chemical identity of the radioactivity in cell nuclei was determined by high performance liquid chromatography in three males and four females. Concentrations of radioactivity in nuclear pellets were highest in the hypothalamus and lowest in the cerebral cortex. This regional variation was highly significant (P less than 0.001), but there was no significant difference between nuclear concentrations of radioactivity in males and females. In supernatant fractions, concentrations of radioactivity showed no significant variation between brain regions and after 60 min, 52-67% of the extracted radioactivity was no longer in the form of [3H]DES. Nuclear levels of radioactivity in pituitary glands and genital tracts of both male and female fetuses were 2-5 times higher than those in hypothalamus. The results demonstrated a direct interaction between DES and cell nuclei from specific regions of the brain, pituitary gland, and genital tract at this stage of gestation in a primate.
为研究合成雌激素己烯雌酚（DES）在发育中的灵长类动物体内可能的作用部位，在妊娠约122天（范围为121 - 124天）时，将[³H]DES（250μCi，静脉注射，或500μCi，皮下注射）直接注入两只恒河猴和九只食蟹猴胎儿体内。60分钟后，通过放射自显影检查积聚放射性的细胞位置，检查了两只雄性和两只雌性胎儿。在雌性胎儿中，在下丘脑、视前区和杏仁核中观察到标记神经元，但在大脑皮层中未观察到。在一只雄性胎儿中观察到类似的摄取模式，但标记神经元的百分比较低，而在另一只雄性胎儿中，在任何区域都几乎未观察到标记。通过高效液相色谱法测定了三只雄性和四只雌性胎儿细胞核中放射性的化学性质。核沉淀中的放射性浓度在下丘脑最高，在大脑皮层最低。这种区域差异非常显著（P < 0.001），但雄性和雌性胎儿细胞核中放射性浓度之间没有显著差异。在上清液组分中，放射性浓度在脑区之间没有显著变化，60分钟后，52 - 67%的提取放射性不再是[³H]DES的形式。雄性和雌性胎儿垂体和生殖道中的核放射性水平比下丘脑中高2 - 5倍。结果表明，在灵长类动物妊娠的这个阶段，DES与大脑、垂体和生殖道特定区域的细胞核之间存在直接相互作用。
