Effects of sodium molybdate on the androgen receptor from the R3327 prostatic tumor.
The present study describes the effects of sodium molybdate on several physicochemical properties of the androgen receptor from the Dunning R3327 prostatic tumor. Molybdate was found to stabilize the steroid-binding activity of the receptor. Maximum binding activity was found with concentrations of 10 mM molybdate or greater. Density gradient and gel filtration analyses of the receptor revealed an 8.5-9.0S, 68A form (mol wt, approximately 265,000-275,000) in either the presence or absence of molybdate (20 mM) when determined under low ionic conditions. Under high ionic conditions (400 mM KCl), the receptor was maintained in a similar form (8.5-9.0S; 72-73A; mol wt, approximately 275,000-295,000) in the presence of molybdate; however, it disaggregated to a smaller 4.4S, 61 A form (mol wt, approximately 120,000) in the absence of molybdate. Affinity labeling of the receptor with 17 beta-[(bromoacetyl)oxy]-[1,2,4,5,6,7,16,17-3H8]5 alpha-androstan-3-one showed a mol wt of 118,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Molybdate inhibited the salt-induced transformation of the receptor to a DNA-binding state, but did not inhibit the DNA binding of the receptor transformed previously in the absence of molybdate. These studies suggest that sodium molybdate stabilizes the steroid-binding activity of the androgen receptor in an aggregated nontransformed state.
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D008297:Male; D008982:Molybdenum / Q000494:pharmacology*; D009994:Osmolar Concentration; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D008982:Molybdenum; D004247:DNA; C024687:sodium molybdate(VI)