Correlative study of the morphology and C19-steroid metabolism of benign and cancerous human prostatic tissue

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Abstract
Perineal punch biopsy specimens of human prostate with benign hyperplasia (BPH), well- and poorly differentiated adenocarcinoma and transitional cell carcinoma were incubated with testosterone-1,2-3H and 5.alpha.-dihydrotestosterone-1,2-3H. Incubations were done using a single tissue-radiosubstrate ratio and time point. Resulting radiosteroid patterns were related to histologic and ultrastructural features of these tissues. Well differentiated neoplasms had ultrastructural characteristics closely resembling hyperplasic epithelia. In BPH and well differentiated carcinomas the C19-steroids were metabolized by the 17.beta.-hydroxysteroid pathway. Cells in poorly differentiated adenocarcinoma and transitional cell carcinoma lacked the cytoplasmic organelles responsible for secretion. Formation of 5.alpha.-reduced 17.beta. hydroxysteroids was decreased in these carcinomas, while conversion to 17-oxosteroid radiometabolites remained unchanged or was increased. These results indicate that loss of prostatic differentiation is attended by a trend from reductive toward oxidative radiotestosterone metabolism. Even in NADPH supplemented preparations of the majority of poorly differentiated tumors there was diminished transformation to 5.alpha.-dihydrotestosterone, the key intracellular hormone in the expression of androgenic activity in the prostate. These findings may explain why poorly differentiated prostatic neoplasms are frequently unresponsive to antiandrogenic therapy.