In vivo and in vitro testosterone metabolism by the androgen insensitive rat

Abstract

The androgen insensitive (tfm) rat is a male pseudohermaphrodite with inherited tissue insensitivity to androgens. To understand the nature of this genetic defect better, in vivo and in vitro testosterone metabolism was studied in preputial glands from tfm as well as normal male and female rats. in vivo studies in normal rats indicated that testosterone metabolism in cytoplasm and nuclei of preputial glands was similar to that of normal prostate. In the tfm rat, testosterone uptake by the preputial gland was normal, but dihydrotestosterone (DHT) was not retained in cytoplasm or nuclei. Reduction of testosterone to DHT by 5α-reductase in tissue slices of eight organs as well as preputial gland cytoplasm and nuclei from tfm rats was indistinguishable from that in normal animals. We conclude that the inability of the tfm rat to retain intracellular DHT is due to a defect of a cytoplasmic binding component which normally concentrates DHT in the cell and facilitates its transfer to the nucleus. Since DHT is believed to be one of the intranuclear effectors of testosterone action, the androgen insensitivity of the tfm rat may be explained by the inability to concentrate this steroid at its presumed site of action.