Characterization by high performance liquid chromatography of nuclear metabolites of testosterone in the brains of male rhesus monkeys.

Testosterone (T) restores the potency of castrated male rhesus monkeys, and our autoradiographic data have demonstrated that 3H-T or its metabolites concentrate in cell nuclei in the corticomedial amygdala, bed nucleus of stria terminalis, preoptic area, and hypothalamus. In rat, 3H-estradiol (3H-E2) is a major nuclear metabolite of 3H-T in areas of the limbic system, but comparable data are lacking for the primate. We have therefore developed an improved technique using high performance liquid chromatography for investigating metabolites of 3H-T that accumulate in cell nuclei in small amounts of tissue obtained from the brain of the rhesus monkey. Two castrated male rhesus monkeys were injected with 5 mCi of 3H-T and were killed 30 min later. In amygdala, preoptic area-bed nucleus of stria terminalis, and hypothalamus, 48-70% of the nuclear radioactivity was in the form of 3H-E2 (Type I tissues). In six other brain areas and in pituitary, 35-85% of the nuclear radioactivity was in the form of 3H-T (Type II tissues), whereas in genital tract tissues, 86-99% of the nuclear radioactivity was in the form of 3'-dihydrotestosterone (3H-DHT) (Type III tissues). In plasma and in supernatants from both Type I and Type II tissues, the proportions of 3H-T were high, and 3H-E2 did not exceed 10% of the total extractable radioactivity. These data suggest that, as in rodents, some of the central actions of T in primates may be mediated by estrogen target neurons.