Androgen receptor in the rabbit liver and apparent translocation to the nucleus in vivo.
The present study demonstrates that the liver of a mammal, the rabbit, contains an androgen receptor. Rabbit liver cytosol or purified nuclei were incubated with the radioactive androgen R-1881 (methyltrienolone). The cytosol of adult female rabbit liver contained androgen-binding sites of high affinity, Kd 0.9 nM, and a capacity of 7000 fmol/g liver or 79 fmol/mg cytosol protein. After partial purification by 35% ammonium sulfate precipitation (AS cytosol), the binding specificity pattern was consistent with that of androgen receptor. Apparent translocation from cytosol to nucleus was examined by administering 100 micrograms nonradioactive R-1881 in vivo. One hour later, almost all of the receptor was detected in liver nuclei. The receptor concentration in purified nuclei, as determined by an exchange procedure, was 2100 fmol/g liver, which is an increase of 6-fold relative to the low levels in nuclei of untreated rabbits. The binding affinity, specificity pattern, and protease sensitivity for the sites in the nucleus after in vivo androgen in general resembled those as AS cytosol binding in untreated liver. Androgen receptors were also present in AS cytosol of the immature female rabbit liver and, in lower concentration, of the intact adult male rabbit. The properties of liver androgen binding are quite different from those of testosterone binding protein present in serum. Accordingly, an androgen binding protein with high affinity and specificity and capable of translocation to the nucleus in vivo has been detected in mammalian liver. An androgen receptor in the mammalian liver may mediate androgen effects on liver function, including modulation of synthesis of selective plasma proteins.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003600:Cytosol / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004963:Estrenes / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure*; D008634:Mersalyl / Q000378:metabolism; D015741:Metribolone; D011817:Rabbits; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D004963:Estrenes; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D015741:Metribolone; D008634:Mersalyl; D004229:Dithiothreitol