title: 4-MAPC, a 5 alpha-reductase inhibitor, reduces rat ventral prostate weight, DNA, and prostatein concentrations.
abstract: Several compounds, such as 4-MAPC (4-methyl-3-oxo-4-aza-5 alpha-pregnane-20- carboxylate), that inhibit conversion of testosterone (T) to dihydrotestosterone (DHT) by 5 alpha-reductase have been demonstrated to reduce prostate size in rats and dogs. The current studies were undertaken to determine if this effect is due to a reduction in cell number, in epithelial cell synthetic activity, or both. Eight-week-old intact rats were treated daily for 14 days with sesame seed oil, 4-MAPC (10 mg/kg), 4-MAPC + testosterone propionate (TP, 1 mg/kg), or 4-MAPC + TP (3 mg/kg). Rats were killed 24 hours after the last injection. In the animals treated only with 4-MAPC, ventral prostate weight was reduced 37%, but the 14% reduction in total DNA was not significant. The mean intraprostatic concentration of prostatein, a major secretory protein, was reduced 45% (P less than 0.05). The 3 mg/kg dose of TP increased ventral prostate weight, prostatein concentrations, and acid phosphatase activity, even though DNA/ventral prostate was similar to that in control animals. These observations indicate that the reduction in ventral prostate weight in adult rats is due in part to a reduction in cell number, but the primary effect was due to a reduction in synthetic activity, and possibly atrophy of the epithelial cells. Furthermore, TP in pharmacologic doses increased ventral prostate weight and synthetic activity without increasing DNA.
authors.affiliation: Department of Veterans Affairs Medical Center, Houston, Texas.
authors.forename: H F
authors.initials: HF
authors.lastname: Ghusn
authors.forename: T C
authors.initials: TC
authors.lastname: Shao
authors.forename: M
authors.initials: M
authors.lastname: Klima
authors.forename: G R
authors.initials: GR
authors.lastname: Cunningham
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000135:Acid Phosphatase / Q000378:metabolism; D000727:Androgen-Binding Protein / Q000032:analysis*; D000818:Animals; D001378:Azasteroids; D004247:DNA / Q000032:analysis* / Q000187:drug effects; D013196:Dihydrotestosterone / Q000032:analysis; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects*; D011278:Pregnanes / Q000494:pharmacology*; D011467:Prostate / Q000033:anatomy & histology* / Q000737:chemistry / Q000187:drug effects; D060789:Prostatein; D051381:Rats; D011919:Rats, Inbred Strains; D060765:Secretoglobins; D013739:Testosterone / Q000032:analysis / Q000097:blood; D014598:Uteroglobin; D060788:Mammaglobin B
chemical_list: D058891:5-alpha Reductase Inhibitors; D000135:Acid Phosphatase; D000727:Androgen-Binding Protein; D001378:Azasteroids; D004247:DNA; D013196:Dihydrotestosterone; D011278:Pregnanes; D060789:Prostatein; D060765:Secretoglobins; D013739:Testosterone; D014598:Uteroglobin; C511484:Scgb1d2 protein, rat; C511483:Scgb1d4 protein, rat; C037399:4-methyl-4-aza-3-oxopregnane-20-carboxylate; C556468:Scgb2a1 protein, rat; D060788:Mammaglobin B