Hormonal regulation of the androgen receptor expression in human prostatic cells in culture.
The regulation of the androgen receptor (AR) expression was studied using immunocytochemical and Western blot techniques on separate cultures of epithelial cells (PNT2) and fibroblasts of human prostate. In both cell types, immunocytochemistry revealed both nuclear and cytoplasmic staining. Treatment with DHT (5 x 10(-9) M) increased both the intensity of nuclear staining and the number of cells stained. The increase, observed after DHT treatment was markedly decreased by cyproterone acetate (5 x 10(-7) M), confirming a direct action of DHT via the AR. This autoregulation of AR was confirmed by Western blot, and seems to involve transcription and protein synthesis, since it was suppressed by actinomycin D and cycloheximide. In fibroblasts, known to contain an estrogen receptor, estradiol treatment (5 x 10(-7) M) also increases the AR immunostaining. In addition, coculture studies show that epithelial cells require the presence of fibroblasts for optimal expression of the AR. These results demonstrate that prostate epithelial cells and fibroblasts have retained in culture, an hormonal sensitivity correlated with the presence of specific receptors and can serve as a model for the study of hormone action in this tissue in normal or pathological conditions.
Blanchere
M
M
Laboratoire de Biochimie B, Hôpital Necker-Enfants Malades, Paris, France.
Berthaut
I
I
Portois
M C
MC
Mestayer
C
C
Mowszowicz
I
I
D000726:Androgen Antagonists / Q000494:pharmacology; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D018920:Coculture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D017373:Cyproterone Acetate / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D003609:Dactinomycin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011944:Receptors, Androgen / Q000096:biosynthesis*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology
D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013629:Tamoxifen; C016601:afimoxifene; D003609:Dactinomycin; D017373:Cyproterone Acetate; D004958:Estradiol; D003513:Cycloheximide