DIRECT AND MEDIATED EFFECTS OF TESTOSTERONE - ANALYSIS OF SEX REVERSED MOSAIC MICE HETEROZYGOUS FOR TESTICULAR FEMINIZATION

Sex reversed mice are XX males carrying on one of their X chromosomes a translocation of the sex determining region of the Y (Cattanach's Sx r factor). The phenotype corresponds to the Klinefelter syndrome in ma n. The X linked Tfm (teslicular feminization) mutation in the mouse is a frame shift in the androgen receptor gene leading to complete andro gen insensitivity. Due to random X inactivation, sex reversed mice het erozygous for Tfm, are mosaics composed of a variable proportion of an drogen insensitive XTfm and androgen sensitive Xi wildtype cells. In t he intersexual genital tract, Tfm cells are maintained as undifferenti ated cells in the epididymal duct. To the distorted prostate lobes and bulbourethral glands they contribute some lobules of indifferent uret hral glands. A large contribution of Tfm cells allows downgrowth of Wo lffian and Mullerian ducts to form a vagina. In the external genitalia the stimulatory effect of testosterone is reduced leading to various degrees of feminization correlating with the proportion of Tfm cells p resent. In the mosaics effects of testosterone, mediated by local grow th factors from the wildtype to the Tfm cells, can be distinguished fr om direct effects expressed only in the wildtype cells. Mediated effec ts are embryonic induction and morphogenesis of male organs and postna tal maintenance of organ structure and proliferation. The direct effec t is cellular differentiation.