Pretreatments with 5 alpha-dihydrotestosterone and the uptake of testosterone by cell nuclei in the brains of male rhesus monkeys.

An in vivo competition method was used in adult male rhesus monkeys to determine if testosterone binds to high affinity binding agents, notably androgen receptors, in brain cell nuclei. Castrated males received 5 alpha-dihydrotestosterone propionate (DHTP, 20 mg, N = 6), testosterone propionate (TP, 100 mg, N = 3) or oil vehicle (controls, N = 6) followed 3 h later by 5 mCi [3H]testosterone [( 3H]T) as an intravenous bolus. Brain and peripheral tissue samples were removed after 60 min, homogenized and separated into supernatant and purified nuclear fractions. Radioactive metabolites of [3H]T [( 3H]estradiol, [3H]DHT) and unchanged [3H]T were identified by high performance liquid chromatography (HPLC). Androgen pretreatments reduced the nuclear uptake of [3H]T by 67-98% in hypothalamus (HYP), preoptic area (POA) and pituitary gland (PIT). This blockade was presumed to be due to prior occupation of nuclear androgen receptors by unlabeled androgens because pretreatments had no effects on levels of [3H]T in supernatants. Since [3H]T was the major radioactive androgen present in brain cell nuclei, results strongly suggested that the principal nuclear androgen receptor ligand in HYP, POA and PIT was unchanged [3H]T rather than [3H]DHT as occurs in the genital tract. In the amygdala the situation was quite different. Here, nuclear concentrations of [3H]T were reduced by 67% following TP pretreatment but were not changed following DHTP pretreatment, indicating a different uptake mechanism in this region that could have particular relevance for testosterone's central actions on behavior.