Androgen Receptor in the Rabbit Liver and Apparent Translocation to the Nucleusin Vivo*

Abstract

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.

Presence of androgen receptors in the hen hypothalamus and pituitary

“…A marked decrease in the androgen binding sites in the soluble fraction with a concomitant in¬ crease in those in the insoluble fraction was found in HPOA, HMEA, and AP of the hens after admin¬ istration of the unlabelled in vivo, whereas the total number of binding sites did not change (Table 2). These findings are consistent with those in mammals (Isomaa et al 1982;Tezón et al 1982;Sheets et al 1985), and suggest that the androgenbinding component existing in the soluble fraction is transferred to the insoluble fraction when enough androgen is given in vivo in the same man¬ ner as proposed in mammals (Gorski et al 1986).…”

Transplantable human prostatic carcinoma (PC‐82) in athymic nude mice. II. Tumor growth and androgen receptors

“…Likewise, studies on the rabbit liver by Sheets et al demonstrated that 1 h after administration of a high dosage of androgen almost all of the AR was detected in liver nuclei [34]. We considered this concept to be valid for human prostatic tissue as well.…”

Reduced Tissue Androgen Receptors in the Congenitally Obese Male Zucker Rat

“…The prostate has long been regarded as a classical androgen sensitive organ; more recently, the liver has been shown to contain the classical androgen receptor (Sheets, Aten, Kates et al 1985;Bannister et al 1985a,b (Boyden & Parmenter, 1983), their livers have morphological changes similar to those seen in the obese Zucker rat and they have reduced liver androgen receptor concentrations (Eagon, Porter, Francavi Ila et al 1985). In the human reduced levels of liver androgen receptor concentrations have been reported in two men with cirrhosis and associated hypogonadism (Bannister et al 1985b).…”