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The Uptake of Tritiated Diethystilbestrol by the Brain, Pituitary Gland, and Genital Tract of the Fetal Macaque: A Combined Chromatographic and Autoradiographic Study^*

Departments of Psychiatry and Anatomy and Cell Biology, Emory University School of Medicine Atlanta, Georgia 30322;
Georgia Mental Health Institute Atlanta, Georgia 30306

Address requests for reprints to: Richard P. Michael, M.D., Department of Psychiatry, Emory University School of Medicine, Georgia Mental Health Institute, 1256 Briarcliff Road NE, Atlanta, Georgia 30306.

To examine the possible sites of action of the synthetic estrogen diethylstilbestrol (DES) in the developing primate, [³H]DES (250 µCi, iv, or 500 µCi, 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 coretx. 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 < 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.

^* This work was supported by USPHS Grant MH-40420 and the Georgia Department of Human Resources. All experimental procedures were performed in accordance with institutional regulations and the NIH Guide for the Care and Use of Laboratory Animals (NIH Publication 85–23, revised 1985).

Received January 16, 1990.