THE MECHANISM OF ANDROGEN METABOLISM IN HYPOTHALAMUS AND PITUITARY GLAND

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-D1 (D = deuterium) and androst-4-ene-3β, 17β-diol-3-D1 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.