The prostate plasma membrane as an androgen receptor.
The pivotal role of the cell nucleus in androgenic control of target organs, such as the prostate, has become increasingly suspect. Equally qualified receptor activities have been found in the cytosol, endoplasmic reticulum, and plasma membrane. It is presently difficult to explain how a sex steroid can manage proliferation, metabolism, biosynthesis and secretion, all through chromatin-directed signals. In my search for a more satisfactory mediator of androgen action, I discovered that the sodium-potassium-dependent ATPase of the prostate plasma membrane binds androgen, and is activated by the hormone's presence to serve as a metabolic pacemaker. This paper is my terminal status report on one aspect of this hypothesis; namely, the nature and site of androgen binding, with clues as to the mode of action. SDS-PAGE indicates that androgen can be bound to the beta-subunit of prostatic Na,K-ATPase. Selective enrichment of the enzyme by reversible coupling to either concanavalin A or a DHT-affinity column support this conclusion. Several studies show the dynamic effect of androgen binding: increased ouabain binding; enhancement of this binding by facilitated phosphorylation; spectroscopic evidence of conformational shifts, possibly consequences of these suggested activities for regulation, especially of metabolism, are examined.
Farnsworth
W E
WE
Department of Biochemistry, Chicago College of Osteopathic Medicine, Downers Grove, IL 60515.
D015113:Androstane-3,17-diol / Q000737:chemistry; D000873:Anthracenes / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D002846:Chromatography, Affinity / Q000379:methods; D003208:Concanavalin A / Q000737:chemistry; D006801:Humans; D008297:Male; D010042:Ouabain / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D010770:Phosphotransferases; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia; D011489:Protein Denaturation; D011944:Receptors, Androgen / Q000302:isolation & purification* / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D000873:Anthracenes; D011944:Receptors, Androgen; D003208:Concanavalin A; D015113:Androstane-3,17-diol; D010042:Ouabain; C013814:anthroylouabain; D010770:Phosphotransferases; D000254:Sodium-Potassium-Exchanging ATPase