The androgen receptor of the prostate plasma membrane - an hypothesis.
The hypothesis that the prostatic plasma membrane sodium pump apparatus functions as a non-genomic androgen receptor is based upon a number of its properties: (1) Androgen enhances the uptake of K(+) into minced rat prostate. (2) Ouabain, a specific inhibitor of Na/K-ATPase activity, strongly opposes the androgenic effect. (3) In non-genomic microsomes, ouabain sensitivity of the enzyme is enhanced by androgen. (4) Kinetic studies show that androgen significantly increases Vmax, Km and energy of activation of the enzyme. (5) Enzyme, treated with [gamma-(32)P]-ATP and then subjected to SDS-PAGE electrophoresis, binds only to its alpha-subunit, but, if treated with [(3)H]-DHT, shows isotope binding to the beta-subunit. (6) [(3)H]-ouabain binding to androgenized enzyme is 5.5 times greater than to the non-androgenized enzyme. (7) Treatment of the enzyme with 10(-9) M DHT enhances by 40% the binding of the ouabain derivative, anthroyl ouabain (AO). (8) Fluorescent spectra appears to show that, upon phosphorylation of the androgenized enzyme, there is a 14% approximation of the two subunits to each other. (9) Except for neuroepithelium, only the epithelium of the prostate has apically located Na/K-ATPase. Preliminary work in other labs suggests that the beta-subunit of the Na/K-ATPase may be required for establishing the polarity of some epithelial cells.
Farnsworth
Wells E
WE
Department of Urology, Feinberg School of Medicine, Northwestern University, 350 W. Schaumburg Road, D-136 Schaumburg, IL 60194, USA. wfa271@merle.it.northwestern.edu
D000728:Androgens / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008962:Models, Theoretical; D032383:Myocytes, Cardiac / Q000378:metabolism; D009420:Nervous System; D010042:Ouabain / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D000728:Androgens; D000873:Anthracenes; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D010042:Ouabain; C013814:anthroylouabain; D000254:Sodium-Potassium-Exchanging ATPase