Effects of two different medical treatments on dihydrotestosterone content and androgen receptors in human benign prostatic hyperplasia.
In order to evaluate the biochemical modifications induced by hormonal treatments on human prostatic tissue, the intracellular distribution of tissue DHT and AR were investigated in BPH patients untreated and treated (25-30 days before surgery) with the association of cyproterone acetate (CPA), 100 mg p.o./day plus tamoxifen (TAM), 100 mg p.o./day, or with flutamide (FLU) alone, 750 mg p.o./day. Dextran-coated charcoal and exchange assay in the presence of sodium molybdates (0.2 M) were used for AR determination, employing methyltrienolone as radioligand in the presence of triamcinolone acetonide. Endogenous DHT was measured by RIA, after ether extraction and purification on celite microcolumns. The treatment with CPA plus TAM led to a detection of cytosol AR (ARc) in 50% of the specimens, while nuclear AR (ARn) were never measurable. The FLU treatment did not modify the incidence of ARc, while ARn was not detectable. The cytosolic and nuclear compartmentalization of DHT was scarcely affected by the combined CPA plus TAM treatment, while FLU treatment induced a prevalent cytosolic localization of DHT (DHTc = 283.2 +/- 24.6 S.E. and DHTn = 1138.4 +/- 98.7 S.E. pg/mg DNA in untreated patients; DHTc = 350.4 +/- 97.7 S.E. and DHTn = 589.7 +/- 154.4 S.E. pg/mg DNA in CPA plus TAM treated patients; DHTc = 1101.7 +/- 165.7 S.E. and DHTn = 733.0 +/- 93.9 S.E. pg/mg DNA in FLU treated patients). Both medical treatments, therefore, were able to reduce prostatic growth on account of the reduced value of nuclear DHT content.
Petrangeli
E
E
Istituto di Clinica Medica V, Universita La Sapienza, Rome, Italy.
Sciarra
F
F
Di Silverio
F
F
Toscano
V
V
Lubrano
C
C
Conti
C
C
Concolino
G
G
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000378:metabolism; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017373:Cyproterone Acetate; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*
D000726:Androgen Antagonists; D000813:Anilides; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013629:Tamoxifen; D017373:Cyproterone Acetate; D005485:Flutamide; D003534:Cyproterone