We have established organ cultures of human prostate for in vitro anal
ysis of the hormone responsiveness of prostatic carcinoma. Tissue samp
les were obtained from total prostatectomies for localized cancer. Nor
mal prostate tissues with age-related hyperplastic changes were obtain
ed from cystoprostatectomies of bladder cancer patients representing t
he same age group, and they were cultivated as controls. The explants
of prostates were cultured for 7 days in basal medium containing 5 % d
extran charcoal-treated fetal calf serum, insulin (0.08 IU/ml), and de
xamethasone (10(-7) M) with or without dihydrotestosterone (DHT) (10(-
7) M) or estradiol (10(-9) M). Control prostates showed involutive cha
nges of morphology when cultured in basal medium. These changes were p
revented by DHT, which also maintained a strong epithelial immunostain
ing for PSA (prostate specific antigen), which was used as a marker fo
r tissue-specific functions. The concentration of PSA in the medium wa
s high. The rate of [H-3]thymidine incorporation into DNA was stimulat
ed by DHT in some cultures of control prostates, but no increase was s
een in the others. Androgen stimulation of [H-3]thymidine incorporatio
n was consistently inhibited by the antihormone cyproterone acetate. T
he main morphological response of cultured control prostates to estrad
iol was induction of squamous metaplasia. This was associated with inc
reased incorporation of [H-3]thymidine, which was radioautographically
localized to the basal layer of epithelium. Estradiol effects were co
unteracted by the antihormone toremifene. The expression of androgen r
eceptor mRNA and protein in cultured control prostate was demonstrated
by Northern blotting and immunohistochemistry, respectively. Also, th
e expression of estrogen receptor was demonstrated by the polymerase c
hain reaction analysis of total mRNA from cultured control and cancer
prostate. The cultured explants of prostate cancer maintained the over
all morphology of the original carcinoma. However, the presence of DHT
improved the morphology of cancerous acini in all better differentiat
ed carcinomas (3 grade I and 5 grade II), and corresponding responses
to DHT were observed in the rate of DNA labeling with [H-3]thymidine.
In 2 of 3 grade I carcinomas, DHT increased DNA synthesis, but in grad
e II cancers the patterns of hormone responses were more variable. The
poorly differentiated grade III prostatic carcinomas did not respond
to either hormone as measured by [H-3]thymidine uptake, and no hormone
effects could be seen in morphology. Immunostaining for PSA differed
from that in control prostates: besides cancerous acini, the surroundi
ng stroma was also intensively stained, which suggests unpolarized and
impaired secretion of PSA by the cancer cells. In conclusion, our stu
dy shows that organ cultures can be used to analyze the hormone respon
siveness and/or biology of normal and malignant human prostate in vitr
o. The results provide a basis for creating a method for in vitro test
ing of the individual hormone and drug responsiveness of a prostate ca
ncer.