Laroque P A, Prahalada S, Molon-Noblot S, Cohen S M, Soper K, Duprat P, Peter C P, van Zwieten M J
Merck Research Laboratories, Merck & Co., Riom, France.
Prostate. 1995 Sep;27(3):121-8. doi: 10.1002/pros.2990270302.
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.
本研究的目的是确定两种不同的5α-还原酶抑制剂（非那雄胺和MK-0434）对增生性犬前列腺腺性和基质成分的影响。在本研究中，犬口服两种化合物中的一种，剂量为1mg/kg/天，持续16周；对照犬接受安慰剂。通过对Masson三色染色切片采用点计数法对前列腺腺性和基质成分的形态学变化进行定量分析。与对照组相比，5α-还原酶抑制剂治疗导致平均前列腺体积显著（P≤0.05）减小、前列腺萎缩的微观证据以及前列腺腺性和基质成分的绝对体积显著（P≤0.05）减小。在非那雄胺治疗的犬中，相对于基线的平均百分比变化为：上皮，-52；管腔，-58；纤维血管基质，-41；平滑肌，-29。在MK-0434治疗的犬中，相对于基线的平均百分比变化为：上皮，-77；管腔，-58；纤维血管基质，-38；平滑肌，-42。MK-0434治疗的犬对腺性成分的作用略大于非那雄胺治疗的犬；然而，对基质的作用相似。这些结果清楚地表明，抑制5α-还原酶活性会影响犬增生性前列腺腺性和基质成分的生长和维持。非那雄胺治疗（保列治）的男性前列腺体积减小可能是由于腺性和基质成分均萎缩。
