Nuclear retinoic acid binding protein in human prostate adenomas.
A retinoic acid binding protein has been detected in salt extracts of nuclei obtained from human prostate adenoma. The binding was characterized by competition experiments, temperature/time studies and saturation analysis. Substantial binding was only observed after sonication of nuclei and charcoal-pretreatment of a salt extract. The binding of radiolabelled all-trans-retinoic acid was displaced by all-trans-retinoic acid, retinol and to a lesser extent retinal and two synthetic retinoids, RO 10-1670 and RO 13-7410. Testosterone and dihydrotestosterone, at a 100-fold excess, had little effect on the binding. The association between retinoic acid and nuclear protein was both temperature and time dependent. At 37 degrees C, equilibrium was rapidly reached (30 min) whereas at 4 and 25 degrees C, ligand binding occurred at a slower rate. Saturation analysis performed under steady-state conditions yielded a dissociation constant of 15 +/- 2 nmol/l. Metabolism studies failed to show conversion of either radiolabelled all-trans-retinol or [3H]retinoic acid in vitro; these data suggest that both acid and alcohol forms of vitamin A are recognized by the extracted nuclear protein. The effect of three enzyme inhibitors on [3H]retinoic acid binding was studied. Binding was unaltered in the presence of aprotinin and phenylmethylsulphonyl fluoride but sodium molybdate (10 mmol/l) increased binding by 18%. The presence of a specific retinoid binding protein in prostate nuclei suggests that retinoids may play some role in the function of the gland.
Boyd
D
D
Chisholm
G D
GD
Habib
F K
FK
D002352:Carrier Proteins / Q000032:analysis*; D002467:Cell Nucleus / Q000032:analysis*; D002606:Charcoal / Q000494:pharmacology; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011869:Radioligand Assay; D018168:Receptors, Retinoic Acid; D013010:Sonication
D002352:Carrier Proteins; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; D002606:Charcoal