Kinetic properties of the 5α-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain

Abstract

The 5α-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5α-eductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5α-reductase has a higher activity in immature animals.This study was performed in order to verify whether the differences in the 5α-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60–90-day-old), immature (23-day-old), and aged (> 20-month-old) male rats.The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 ± 0.2, 2.72 ± 0.73 and 3.83 ± 0.49 μM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 ± 5.54), in the white matter (19.57 ± 2.36) and in the cerebral cortex (6.47 ± 1.03 ng/h/mg protein) of adult animals have been found to be consistently different.Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 ± 0.11 and 3.39 ± 0.75 μM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 ± 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 ± 5.54); a Vmax (34.31 ± 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats.