Differences in Brain Uptake and Metabolism of Testosterone in Gonadectomized, Adrenalectomized Male and Female Rhesus Monkeys*

Abstract

The possibility that there are sexual differences in the pattern of brain uptake and metabolism of testosterone (T) was examined in five male and five female adult rhesus monkeys (Macaca mulatto). Males and females were gonadectomized 36 h and 1 month, respectively, before infusing [³H]T. All animals were adrenalectomized immediately before the infusion. While animals were anesthetized, [³H]T was infused into the heart at a constant rate for 4 h. During this time blood samples were taken from the carotid artery and internal jugular vein. At the end of the infusion the brain was removed, and the following regions were dissected: anterior pituitary, preoptic area, medial basal hypothalamus, lateral hypothalamus, thalamus, hippocampus, septum, amygdala, cerebellum, and cerebral cortex. Blood and brain samples were analyzed subsequently for radioactive T, 5α-dihydrotestosterone, androstenedione, 5α-androstane-3,17-dione (5αA), 17β-estradiol, and estrone (E₁i). By 4 h there was no difference in circulating ³H-labeled hormone levels across the brain, indicating that a steady state had been reached in that organ. As expressed by the tissue to blood ratio of steroid levels, higher concentrations of T and its metabolites were noted in the male than in the female brain. Activity also was more segregated in the male, notably in areas concerned with reproductive phenomena. This was in contrast to the female in which activity tended to be more diffuse. The metabolism of T was greater throughout the male brain as indicated by the lower percentage of T that was recovered and by the higher percentage of metabolites other than 5αA and E₁. The percentage of 5αA was greater in females, whereas no sex difference in E₁ was found. These data illustrate male-female differences in the metabolism of T and the retention of T and its metabolites, especially in those areas of the brain where these hormones may have their greatst influence. Such differences may be attributed to the exposure of the males to androgens as adults or to sex differences in the organization of the central nervous system.