Effect of aromatase inhibitor, TZA-2209, on the prostate of androstenedione-treated castrated dogs: changes in prostate volume and histopathological findings.
To determine whether the inhibition of estrogen-related effect in the prostate would be of value in the management of benign prostate hyperplasia (BPH), we examined the effect of TZA-2209, a new steroidal aromatase inhibitor, on the prostate in three of six castrated beagles that received 75 mg/week androstenedione. The three other animals served as controls. Sequential measurements of prostate volume by transrectal ultrasonography showed that the volume in TZA-treated dogs was significantly decreased compared with that in the controls. Prostatic aromatase activity was suppressed by TZA administration. Histopathologically, the stromal component was increased and glands were atrophied by androstenedione treatment. TZA administration increased the volume of the glands. Immunohistochemical detection of estramustine-binding protein showed more positive staining of the protein in the glands that were increased in volume by TZA administration. We concluded that the aromatase inhibitor effectively antagonized the estrogen-related stromal changes, however, this action was accompanied by stimulation of the glandular component due to the accumulation of androgens, the substrate of the aromatase. In the light of these findings, we suggest the simultaneous treatment for the androgen-glandular component route in the prostate is necessary for the effective management of BPH.
Suzuki
K
K
Department of Urology, Gunma University School of Medicine, Japan.
Ito
K
K
Tamura
Y
Y
Suzuki
T
T
Honma
S
S
Yamanaka
H
H
D000735:Androstenedione / Q000037:antagonists & inhibitors*; D000818:Animals; D047072:Aromatase Inhibitors; D002352:Carrier Proteins / Q000276:immunology; D002369:Castration; D004285:Dogs; D004961:Estramustine; D007124:Immunoenzyme Techniques; D008297:Male; D009929:Organ Size; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D029584:Prostatic Secretory Proteins; D017154:Stromal Cells / Q000187:drug effects; D013738:Testolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D047072:Aromatase Inhibitors; D002352:Carrier Proteins; D029584:Prostatic Secretory Proteins; C099103:TZA 2209; C028321:estramustine-binding protein; D004961:Estramustine; D000735:Androstenedione; D013738:Testolactone