Testosterone metabolites associated with cytosol receptors and nuclei of anterior pituitary and various brain regions.

Abstract

Abstract Radioactive metabolites bound to the cytosol receptors and nuclei of the anterior pituitary and various brain regions were analyzed 15 min and 60min after [3H]-testosterone (T) administration in the functionally hepatectomized and eviscerated rats. It was clearly demonstrated that there was the thermolabile saturable binding protein for T and its metabolites in the cytosol of the pituitary and brain tissues. With regard to the patterns of T metabolites bound to the cytosol receptor at 15 min after [3H]-T administration, the most predominant metabolite was unchanged T and the remainder was 5α-dihydro-testosterone (DHT) in all brain regions. At 60 min after [3H]-T administration unchanged T also represented the largest portion of radioactivity bound to the cytosol receptor, and DHT accounted for 17.3–11.6% of radioactivity, with the highest percentage in anterior pituitary. Estradiol 17β (E2) accounted for the significant radioactivity in the preoptic area, hypothalamus, and other limbic systems. No significant radioactivity was detected in the metabolites other than T, DHT and E2 in the cytosol receptor bound fractions of all brain tissues. No sexual difference was observed in the levels and distributions of T metabolites bound to the cytosol receptors of anterior pituitary and various brain regions. The patterns of T metabolites associated with the purified nuclei were comparable to those of the cytosol receptor bound fractions in all brain regions. That is, unchanged T was the most predominant metabolite incorporated into nuclei in all brain regions. Percent distribution of DHT was 24.8–5.8% of radioactivity associated with the nuclei, with the highest percentage in anterior pituitary, which has been reported to have the highest 5α reductase activity in the brain tissues. In the preoptic area, E2 represented the greater portion (36.8%) of radioactivity associated with the nucleus than in the other regions. This finding supported the hypothesis that E2 might play the major role on the androgen induced sexual events in this area. The levels of radioactive metabolites associated with the nuclear protein 60 min after [3H]-T administration was the highest in anterior pituitary followed by hypothalamus, preoptic area amygdala and cortex.