5 alpha-reductase, aromatase, and androgen receptor levels in the monkey brain during fetal development.

Abstract

To elucidate the metabolic fate and possible role of androgens and their derivatives during primate fetal development, aromatase (AROM), 5 alpha-reductase (5 alpha R), and androgen receptor (AR; cytosolic) levels were assessed in the brain, heart (HRT), lung (LNG), and skeletal muscle (MUS) of fetal rhesus monkeys. Analyses were performed on tissues taken on days 100 and 160 postconception. Five male and four or five female fetuses were examined at each stage. Brain tissues analyzed included medial basal hypothalamus (MBH), amygdala (AMG), cerebellum (CB), corpus callosum (CAL; splenial region), cerebral cortex (CTX), and cingulate cortex (CNG). In the following, enzyme activities are reported as picomoles per mg protein/h, while receptor levels are femtomoles per mg protein. 5 alpha R activity was measurable in all tissues. Analysis of variance revealed significant tissue differences [P less than 0.001, combined stages and sexes; CAL (2.05) greater than MBH (1.08) greater than AMG (0.63) greater than CB (0.4)-CNG-CTX-LNG-HRT-MUS (0.02); -indicates not significantly different]. A significant age x tissue interaction (P less than 0.001) was noted which could be explained by higher MBH and CAL levels in older vs. younger fetuses and higher AMG levels in younger vs. older fetuses. There was also a significant sex x tissue interaction which was attributed to higher female values in the MBH and CAL. AROM activity was detected in all tissues. Levels varied significantly among tissues [P less than 0.001, combined stages and sexes; MBH (0.80)-AMG (0.76) greater than CAL (0.4)-CNG-CB-CTX-LNG-HRT-MUS (0.07)]. Significant age (P less than 0.001) and age x tissue (P less than 0.001) effects were noted, which were due to higher MBH and AMG levels in younger vs. older fetuses. No sex difference in AROM levels was evident in any tissue. AR was measurable in all cases. Although stage and sex differences were not significant, tissue levels varied significantly [P less than 0.001; LNG (2.8)-MUS (2.6)-MBH (2.2) greater than HRT-AMG-CB-CTX-CAL-CNG (0.9)]. These findings indicate that neural and nonneural fetal primate tissues have the potential for transforming androgens to products that could have greater or lesser biological activity. AR were also noted through which dihydrotestosterone or testosterone could effect a genomic response. Since stage, tissue, and sex differences were evident in neural tissues, metabolic and receptor activities may be important for the normal differentiation of sexually dimorphic behavioral systems in monkeys as well as for potential teratogenic changes under abnormal metabolic or physiological conditions.