Interconversion of androgen receptor forms by divalent cations and 8 S androgen receptor-promoting factor. Effects of Zn2+, Cd2+, Ca2+, and Mg2+.
The effects of divalent cations (Zn2+, Cd2+, Ca2+, Mg2+) on the cytosol androgen receptor were determined by sedimentation into sucrose gradients. At low ionic strength (25 mM KCl, 50 mM Tris, pH 7.4), Zn2+ (200 microM total, which calculates to 130 nM free Zn2+ in 10 mM mercaptoethanol) causes a shift in the sedimentation coefficient of the rat Dunning prostate tumor (R3327H) cytosol receptor and rat ventral prostate cytosol receptor from 7.5 +/- 0.3 S to 8.6 +/- 0.3 S. Zn2+ stabilizes the 8.6 S receptor form in salt concentrations up to 0.15 M KCl in 50 mM Tris, pH 7.2. In low ionic strength gradients containing Ca2+ (greater than or equal to 200 microM) or Mg2+ (greater than or equal to 1 mM), the receptor sediments as 4.7 +/- 0.3 S. The dissociating effects of Ca2+ and Mg2+ can be fully reversed by sedimentation into gradients containing Zn2+ (200 microM total) or Cd2+ (10 microM total). In the presence of Zn2+ (200 microM total), Ca2+ (10 microM to 3 mM) converts the receptor to an intermediate form with sedimentation coefficient 6.2 +/- 0.2 S, Stokes radius 73 A, and apparent Mr approximately 203,000. The potentiating effect of Zn2+ on formation of the 8.6 S receptor (in the absence of Ca2+) and the 6.2 S receptor (in the presence of Ca2+) requires both the 4.5 S receptor and the 8 S androgen receptor-promoting factor. Sodium molybdate stabilizes the untransformed cytosol receptor but, unlike Zn2+, does not promote reconstitution of the 8.6 S receptor from its partially purified components. These results indicate that divalent cations alter the molecular size of the androgen receptor in vitro and thus may have a role in altering the state of transformation of the receptor.
D000645:Ammonium Sulfate / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D011232:Chemical Precipitation; D003600:Cytosol / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000494:pharmacology*; D008623:Mercaptoethanol / Q000494:pharmacology; D008970:Molecular Weight; D008982:Molybdenum / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011944:Receptors, Androgen / Q000032:analysis / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology*
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D002104:Cadmium; D008623:Mercaptoethanol; D011189:Potassium Chloride; D008982:Molybdenum; C024687:sodium molybdate(VI); D008274:Magnesium; D015032:Zinc; D000645:Ammonium Sulfate; D002118:Calcium