Testosterone 5α-reductase activity in neural tissue of fetal rhesus macaques

After development of a 5α-reductase activity (5α-RA) assay based on the capacity of microsomes to convert [³H]testosterone (T) to [³H]dihydrotestosterone (DHT), we analyzed 5α-RA in neural tissues of fetal rhesus macaques at 50, 80 and 150 days of gestation. This method allowed us to collect kinetic data on the properties of the 5α-reductase resident in fetal brain at 150 days of gestation. The K_m and V_max calculated from these data were 4.32μM and 22.6nmol·mg protein^-1· h^-1, respectively. Analyses of 5α-RA in microsomes from the hypothalamic-preoptic area-amygdala (HPA) at dilutions of 1 25 and 1 50 indicated higher enzyme activity with increasing dilution of the microsomes. Measurement of 5α-RA using concentrations of [³H]T which saturated the enzyme in diencephalon (DIEN), brain stem (B.STEM), temporal (TCTX) and frontal cortex (FCTX) of six 50-day old fetuses (3 males and 3 females) revealed no obvious sex differences in 5α-RA, however, a significant difference (P < 0.05) between tissues was noted. The DIEN and B.STEM contained significantly (P < 0.05) higher levels 5α-RA than the FCTX while the TCTX contained an intermediate level of activity. Significant increases in 5α-RA were observed in FCTX and TCTX with time of gestation (50, 80 and 150 days). Other tisues, including amygdala, hippocampus, cerebellum, tegmentum and septum also change with fetal age. These data demonstrate the existence of 5α-reductase in the fetal monkey brain. Significant changes in cortical 5α-RA suggest some role for 5α-reductase in development.