The interaction of testosterone with the brain of the orchidectomized primate fetus

At certain times during gestation, the testes of the fetal macaque produce plasma levels of testosterone (T) that are similar to those of adults. It is thought that testosterone acts on the brain via estrogen and androgen receptors to organize the development of sexually dimorphic neural structures that underlie sex differences in behavior. To test the proposition that there are male-female differences in the occupation of steroid receptor binding sites during fetal development in the cynomolgus macaque, we have compared the uptake of [³H]T and its metabolites in: (1) 5 intact males (plasma T 571.2 ± 215.5ng/100ml); (2) 5 intact females (33.8 ± 25.2 ng/100 ml); (3) in 5 males orchidectomized in utero (14.6 ± 5.7ng/100ml). About 1 week after fetal gonadectomy or sham-operation, all fetuses were given 500 μ Ci [³H]T s.c. and were then delivered 60 min later by Cesarian section. Brains were removed and dissected into blocks containing the hypothalamus and preoptic area, amygdala, hippocampus, and midbrain. Samples of cerebral and cerebellar cortex were also obtained. Purified nuclear pellets were prepared by centrifugation through 2 M sucrose and were extracted into ether and analyzed by high performance liquid chromatography. Hypothalamic nuclear concentrations of [³H]E₂ in intact males (847 ± 195dpm per mg DNA) were significantly lower than those in sham-operated females (2147 ± 542dpm per mg DNA) (p < 0.05), but those in orchidectomized males (2233 ± 345dpm per mg D DNA) were similar to concentrations in females. Thus, fetal gonadectomy abolished the differences between males and females, supporting the hypothesis that the occupation of estrogen receptors is greater in intact male than in intact female fetuses at this stage of gestation. This differences might account for some of T's organizational effects on primate physiology and behavior.