Quantitative evaluation of glandular and stromal compartments in hyperplastic dog prostates: effect of 5-alpha reductase inhibitors.
The objective of this study was to determine the effects of 2 different 5-alpha reductase inhibitors (finasteride and MK-0434) on the glandular and stromal compartments of hyperplastic canine prostates. In this study, dogs received 1 of the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs received a placebo. The morphological changes in the glandular and stromal compartments in the prostate were quantitated by a point-counting method on Masson's trichrome-stained sections. Treatment with 5-alpha reductase inhibitors resulted in significant (P < or = 0.05) decreases in mean prostatic volumes, microscopic evidence of prostatic atrophy, and significant (P < or = 0.05) decreases in the absolute volumes of the prostatic glandular and stromal compartments compared to controls. In finasteride-treated dogs, the mean percent change from baseline was: epithelium, -52; lumens, -58; fibrovascular stroma, -41; and smooth muscle, -29. In MK-0434-treated dogs, the mean percent change from baseline was: epithelium, -77; lumens, -58; fibrovascular stroma, -38; and smooth muscle, -42. The effect on the glandular compartment in dogs treated with MK-0434 was slightly greater than in dogs treated with finasteride; however, the effect on the stroma was similar. These results clearly demonstrate that inhibition of 5-alpha reductase enzyme activity affects growth and maintenance of both glandular and stromal compartments of dog hyperplastic prostates. It is likely that the decrease in size of the prostate in finasteride-treated (Proscar) men is due to shrinkage of both glandular and stromal compartments.
Laroque
P A
PA
Merck Research Laboratories, Merck & Co., Riom, France.
Prahalada
S
S
Molon-Noblot
S
S
Cohen
S M
SM
Soper
K
K
Duprat
P
P
Peter
C P
CP
van Zwieten
M J
MJ
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000502:physiology; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D018120:Finasteride / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000473:pathology*; D011897:Random Allocation; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
C088478:17 beta-benzoyl-4-aza-5 alpha-androst-1-ene-3-one; D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase