COMPARISONS OF THE NUCLEAR UPTAKE OF [H-3] TESTOSTERONE AND ITS METABOLITES BY THE BRAINS OF MALE AND FEMALE MACAQUE FETUSES AT 122 DAYS OF GESTATION

Testosterone secreted by the testis of the macaque fetus is thought to influence certain aspects of the brain’s subsequent development which may be responsible for the ontogeny of sexually dimorphic patterns of behavior. To compare the interactions between testosterone and the receptors for androgens and estrogens in brain cell nuclei in the two sexes, 7 intact female fetuses and 5 intact male fetuses were injected in utero at about 120 days of gestation with [3H]-testosterone (250 μCi i.v. or 500 μCi s.c). One hour later, fetuses were delivered by cesarian section, and samples of brain and peripheral tissues were homogenized and separated into purified nuclear and supernatant fractions. Fractions were analyzed by high performance liquid chromatography to measure levels of [3H]-testosterone and its metabolites. Concentrations of radioactivity extracted from cell nuclei were significantly higher in the hypothalamus-preoptic area than in other brain areas (p < 0.00l); [3H]-estradiol represented 65.0 ± 5.7% of this radioactivity and nuclear concentrations of this metabolite were 73% lower in males than in females (p < 0.001). Nuclear concentrations of [3H]-testosterone in the pituitary gland (68.9 ± 8.8% of extracted radioactivity) were 48% lower in males than in females (p < 0.001). There was no evidence of a sex difference in the tissue uptake of radioactive steroids from blood, but in males, levels of endogenous plasma testosterone (599.8 ± 208.2 ng/100 ml) were significantly higher than in females (37.7 ± 28.5 ng/100 ml: p < 0.01), and the specific activity of [3H)-testosterone in blood was consequently lower in males than in females. For this dilution to have reduced the nuclear uptake of radioactive steroid, the binding must have been close to saturation, implying that nuclear estrogen-binding sites in males were substantially occupied by endogenous steroids. This is the first evidence of a major difference in the nuclear uptake of a gonadal hormone by the brains of male and female primate fetuses. © 1990 S. Karger AG, Basel.