Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture.
We have adopted an in vitro three-dimensional histoculture technique for assay of androgen sensitivity in explants of human benign prostatic tissue. The assay is based on the uptake of 3H-thymidine/micrograms protein in explants of prostate incubated in parallel with dihydrotestosterone (DHT) and hydroxyflutamide (HF) controls. The ratio of 3H-thymidine/micrograms protein in DHT treated samples per 3H-thymidine/micrograms protein in HF treated samples provides an index of androgen sensitivity. The DHT/HF index measured in 24 BPH specimens averaged 3.6. To determine the specificity of the HF effect, we measured the DHT/HF index in a single prostate at different concentrations of HF in the presence of fixed concentrations of DHT (2 x 10(-8) M) and noted a dose-response relationship. In addition we noted no effects of HF on 3H-thymidine incorporation over a range of 2 x 10(-4)M compared to 2 x 10(-7)M, except at the highest concentration. Of surprise was the finding of an average DHT/HF index in 5 different nonprostate tissues, including breast, uterus, colon, kidney, and thyroid, that was similar to the index found in prostates. We plan to adapt this androgen sensitivity assay to measure the DHT/HF index in biopsy-size samples of prostate, since such an assay could then be utilized to determine androgen sensitivity in individual patients with prostate cancer.
D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D006652:Histological Techniques; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D013936:Thymidine / Q000493:pharmacokinetics
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D005485:Flutamide; D013936:Thymidine