Correlated biochemical and stereological studies on testosterone metabolism in the stromal and epithelial compartment of human benign prostatic hyperplasia.
The growth and function of the human prostate is dependent upon a continuous supply of androgens, mainly 5 alpha-dihydrotestosterone, the 5 alpha-reduced metabolite of testosterone. Within the human prostate dihydrotestosterone is thought to be the intracellular mediator of androgen action. Although it is well documented that dihydrotestosterone is evenly distributed between the stromal and epithelial compartment of the prostate, the anatomical localization of dihydrotestosterone formation within the normal and hyperplastic prostate is still not established. To provide further insight into this problem we have measured, under conditions approximating the in vivo state, dihydrotestosterone formation in prostates obtained from 4 men with normal prostates and 36 men with benign prostatic hyperplasia. In addition to this we have performed histometric analysis of the cellular composition of the samples incubated, in order to correlate the morphological and the histochemical findings. Dihydrotestosterone is the major metabolite, and androstanediol and androstenedione were formed in smaller quantities. Under the given conditions metabolite formation from testosterone increased linearly for 60 minutes and the half maximum rate of dihydrotestosterone formation (Km) was observed at about 1.25 X 10(-6) M testosterone, a value similar to that reported for rat prostatic nuclei and human prostatic tissue. Dihydrotestosterone formation was higher in hyperplastic prostates than in the normal prostate. (Student's t test: p less than 0.05). The stroma in both the normal and hyperplastic tissue converts testosterone to dihydrotestosterone very actively. No significant relation was found between dihydrotestosterone formation and the per cent distribution of the stromal and epithelial compartment in any sample studied. In conclusion, our results are compatible first with the thesis that the rate of dihydrotestosterone formation is increased in the hyperplastic prostate and secondly with the concept that the rate of dihydrotestosterone formation is approximately the same in the epithelial and stromal compartments of the prostate.
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HU
Schweikert
P
P
Totzauer
H P
HP
Rohr
G
G
Bartsch
D015113:Androstane-3,17-diol / Q000096:biosynthesis; D002855:Chromatography, Thin Layer; D013196:Dihydrotestosterone / Q000096:biosynthesis*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D013196:Dihydrotestosterone; D014316:Tritium; D015113:Androstane-3,17-diol; D013739:Testosterone