A comparison of the effects of castration and 6-methylene progesterone, a 5 alpha-reductase inhibitor, on the rat ventral prostate.
6-Methylene progesterone (6MP) is an irreversible in vitro kcat inhibitor of rat prostate 5 alpha-reductase, the enzyme which converts testosterone (T) to dihydrotestosterone (DHT). Treatment of adult rats with 6MP or diethylstilbestrol (DES) decreased the weight of the ventral prostate (VP) by 45%, while castration reduced it by 86%. Histologically, the 6MP-treated VP were indistinguishable from those of controls, while the VP from DES-treated rats showed fibrous stromal hypertrophy as in castrated rats. The prostatic hydroxyproline content, an index of collagen levels, was enhanced by castration or DES, but was not significantly increased by 6MP. Within 2 days of 6MP treatment, the 5 alpha-reductase activity was reduced by 46% and ornithine decarboxylase (ODC) activity was lowered by 27%. During this time the prostatic acid phosphatase activity increased 42% and remained elevated with continued exposure to 6MP up to 13 days. The castration-induced involution of the VP was accompanied by a reduction in serum T and an increase in serum luteinizing hormone (LH). 6MP had no effect on T and LH serum levels but reduced the DHT content within the VP by 64%. Our results indicate that the structure and secretory acid phosphatase activity of the VP are less sensitive to changes in the ratio of T:DHT than is cell proliferation. Thus, the relative amounts of DHT and T within the VP may prove to be more significant than the absolute amount of either androgen in controlling prostate growth or its attendant neoplasms.
Department of Physiology, Duke University Medical Center, Durham, NC 27710.
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D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011374:Progesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011467:Prostate / Q000033:anatomy & histology* / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013739:Testosterone / Q000097:blood
D058891:5-alpha Reductase Inhibitors; C036790:6-methylene-4-pregnene-3,20-dione; D013739:Testosterone; D011374:Progesterone; D004054:Diethylstilbestrol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000135:Acid Phosphatase; D009955:Ornithine Decarboxylase; D006909:Hydroxyproline