The role of androgen receptors in sexual differentiation of the brain: Effects of the testicular feminization (Tfm) gene on androgen metabolism, binding, and action in the mouse

Abstract

The effects of the testicular feminization (Tfm) mutation on androgen metabolism, binding, and action were studied in the mouse. Cytosolic binding of [3H] dihydrotesterone (DHT) was reduced by approximately 90% in the brains, pituitaries, submaxillary glands, and kidneys of Tfin/Y males, as compared to wild-type male controls. Nuclear [3H] DHT binding was abolished in tissues from Tfm male animals. Implantation of testosterone-containing (T-containing) Silastic capsules elevated nuclear estrogen receptor (ERn) concentrations to a similar extent in the brains of all four genotypes studied (normal males, Tfm-affected males, normal females, and Tfm carrier females). Administration of T to normal males led to elevations of cytosolic progestin receptors (PRc) and monoamine oxidase (MAO) activity in the brain, and of alcohol dehydrogenase (ADH) and glucose-6-phosphate dehydrogenase (G6PDH) in the kidney. In Tfm-affected males, only the PRc response to T was observed, at a somewhat reduced level compared to that in normal male and female controls: no effect of T was observed with respect to either MAO in the brain, or ADH and G6PDH activities in the kidney. Estradiol (E2) administration increased the activity of pituitary G6PDH and lactic dehydrogenase (LDH) in all four genotypes. However, brain MAO activity was increased by E2only in normal and carrier females. The lack of an MAO response to E2 in Tfm-affected males is consistent with the hypothesis that the central nervous system of this genotype is at least partially masculinized, despite the loss of androgen receptor-mediated responses—most probably as a result of local conversion of T to E2 within the brain itself. © 1988, Psychonomic Society, Inc.. All rights reserved.