Correlative study of the morphology and C19-steroid metabolism of benign and cancerous human prostatic tissue.
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 5alpha-dihydrotestosterone-1,2-3H. Incubations were carried out 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 hyperplastic epithelia. Both in BPH and in well differentiated carcinomas the C19-steroids were mainly metabolized by the 17beta-hydroxysteroid pathway. In contrast, cells in poorly-differentiated adenocarcinoma and transitional-cell carcinoma lacked the cytoplasmic organelles responsible for secretion; formation of 5alpha-reduced 17beta-hydroxysteroids was decreased in these carcinomas, while conversion to 17-oxosteroid radiometabolites remained unchanged or was greatly increased. These results indicate that loss of prostatic differentiation is attended by a trend from reductive toward oxidative radiotestosterone metabolism. Even in NAPDH-supplemented preparations of the majority of poorly-differentiated tumors, there was diminished transformation to 5alpha-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 anti-androgenic therapy.
D000728:Androgens / Q000378:metabolism*; D015113:Androstane-3,17-diol / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione