In order to investigate the metabolism and mechanism of action of testosterone in the central nervous system, the following experiments were performed :
1. The pathway of testosterone metabolism in the anterior pituitary and the hypothalamus of male Wistar rats was analyzed using GC-MS. Main metabolites were identified as androst-4-ene-3, 17-dione, 5α-androstan-17β-ol-3-one, 5α-androstane-3α, 17β-diol, 5α-androstane-3β, 17β-diol, androst-4-ene-3α, 17β-diol and androst-4-ene-3β, 17β-diol.
2. The metabolism of androst-4-ene-diol into 5α-androstanediol in the CNS was then analyzed using androst-4-ene-3α, 17β-diol-3-D
1 (D = deuterium) and androst-4-ene-3β, 17β-diol-3-D
1 as the incubation substrate. Twenty to thirty percent of androst-4-ene-3α, 17β-diol was converted directly into 5α-androstane-3α, 17β-diol, but androst-4-ene-3β, 17β-diol was not converted into 5α-androstane-3β, 17β-diol.
3. Change in 5α-reductase activity in the CNS after castration was analyzed by measuring the amount of 5α-reduced metabolites (5α-DHT & 5α-androstanediol) formed by the incubation of testosterone-
14C with a homogenate of the CNS tissues.
It was evident that the 5α-reductase activity of the pituitary increased 5-fold at 5 weeks after castration, but in the hypothalamus no significant change was recognized.
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