Selective activation of androgen receptors in the subcortical brain of male cynomolgus macaques by physiological hormone levels and its relationship to androgen-dependent aromatase activity.

Abstract

Aromatase activity (AA) is androgen dependent and independent in subcortical regions of the nonhuman primate brain, but the correlation of androgen receptor (AR) content with AA has not been demonstrated. Thus, we castrated 10 adult male cynomolgus monkeys (Macaca fascicularis) and divided them into 2 groups. One group (n = 6) received empty Silastic capsules, whereas the second group (n = 4) received Silastic capsules filled with testosterone (T). Animals were killed after 3 weeks. Microsomal AA and cytosolic and nuclear AR were determined in specific brain regions dissected from frozen sections. Sera from T-treated subjects contained T, dihydrotestosterone, and LH levels that were not significantly different from the precastration amounts (P < 0.05). Cytosolic AR concentrations declined after T treatment in 12 of 20 brain areas studied (P < 0.05). Nuclear AR levels, on the other hand, were significantly elevated after T treatment (activated) only in the ventral medial nucleus (VMN) and infundibular nucleus/median eminence (P < 0.05). AA distribution was significantly different (P < 0.05) among 20 brain nuclei and subregions. The highest activities were found in the bed nucleus of the stria terminalis, the medial preoptic area, the medial and cortical amygdala, and the VMN. Lesser activities were found in other brain regions. Physiological concentrations of T increased AA only in the VMN and infundibular nucleus-median eminence (P < 0.05). These data suggest that physiological levels of androgens are effective in regulating AA only in those brain areas in which AR are activated.