Testosterone metabolism in peripheral nerves: Presence of the 5α-reductase-3α-hydroxysteroid-dehydrogenase enzymatic system in the sciatic nerve of adult and aged rats

Abstract

Previous reports from this laboratory indicate that the 5α-reductase, the enzyme which converts testosterone into its “active” metabolite 5α-androstan-17β-ol-3-one (dihydrotestosterone, DHT) is highly concentrated in the white matter structures of the CNS, which are mainly composed of myelinated fibers. No studies have been performed up to now, in order to evaluate the possible presence of the 5α-reductase activity in peripheral myelinated nerves. To this purpose the 5α-reductase activity has been evaluated in the sciatic nerve of the rat and compared to that present in the cerebral cortex and in the subcortical white matter, a central structure mainly composed of myelinated fibers. The study has been performed in normal adult male rats (60–90-day-old) and in aged (20-month-old) animals. The data obtained in 60–90-day-old animals indicate the presence of an active metabolism of testosterone at the level of the sciatic nerve. In this structure, testosterone is actively transformed into DHT and 5α-androstan-3α, 17β-diol (3α-diol); in the sciatic nerve, the formation of DHT is equal to that found in the subcortical white matter and higher than that found in the cerebral cortex. Moreover, at variance with what happens in CNS structures, where 3α-diol is produced only in small amounts, in the sciatic nerve this metabolite is produced in amounts similar to those of DHT. The study in aged rats has shown that in the sciatic nerve, the formation of DHT and particularly that of 3α-diol are much lower than in younger animals. No age-related variations in the 5α-reductase activity in the cerebral cortex and in the subcortical white matter have been observed.