In vitro Aromatization and Other Androgen Transformations in the Brain of the Hamster (Mesocricetus auratus)1

Abstract

Pathways of androgen metabolism were studied in hamster brain to determine whether the actions of circulating androgens on behavior and neuroendocrine responses could be mediated by conversion to estrogen or other metabolites. Anterior limbic cortex (LIM), preoptic area/hypothalamus (POA/HTH), frontal cerebral cortex, gonads and muscle were pooled from 4 groups of animals: control males and females and blinded males and females. Tissue homogenates were incubated for 60 min at 37°C with [³H]-androstenedione in the presence of an NADH-NADPH generating system. After extraction and chromatography, products were identified by reverse isotope dilution and recrystallization to constant specific activity. Estrone (E₁) was synthesized in incubates of LIM and POA/HTH from all 4 groups; ovarian tissue synthesized both E₁ and estradiol-17β(E₂ β). No aromatase activity was detectable in cerebral cortex, muscle or testis. All brain and ovarian incubates contained 5α-androstane-3,17-dione but a 5β-reduced metabolite, 5β-androstane-3,17-dione was present in even larger amounts. No 17β- or 17α-oxidoreductase activity was identified in brain samples in these experiments; however, substantial quantities of radioactivity, possibly polyhydroxylated androgens, remained unidentified. These experiments demonstrate that aromatase and 5α-reductase, 2 enzymes leading to the synthesis of biologically active metabolites, are present in steroid target areas of the hamster CNS. Further, substantial 5β-reductase activity is present, although a biological function for 5β-reduced androgens in this species has not been reported.