Experimentally-induced prostatic hyperplasia in young beagles: a model to evaluate the chemotherapeutic effects of gossypol.
This study investigated the effect of gossypol on hyperplastic canine prostates induced with long-term administration of androgen and estrogen. Twelve 16-week-old male beagle dogs were divided evenly (n = 3) into 4 treatment groups: (1) CONTROL: vehicle only; (2) Gossypol-Treated: 20 mg/kg gossypol acetic acid; (3) Steroid-Induced: 4 mg/kg testosterone and 40 micrograms/kg estradiol-17 beta; (4) Gossypol-Treated and Steroid-Induced: 4 mg/kg testosterone, 40 micrograms/kg estradiol-17 beta and 20 mg/kg gossypol. The subjects received treatments every other day for 1 month. The beagles treated with steroids developed an acute enlargement (approximately 10-fold) of the prostate as compared to control. The prostatic acini were underdeveloped and characterized by simple squamous to low cuboidal epithelium in the control subjects while acini in steroid-induced subjects were characterized by simple tall columnar epithelium. The subjects treated with gossypol had prostates histologically similar to controls with the exception of loosened periurethral connective tissue. Serum testosterone and estradiol-17 beta levels imply that gossypol can reduce steroid hormonal levels. Mean serum testosterone levels in gossypol-treated subjects were reduced approximately 50% from controls. Serum biochemistry profiles indicate that steroid and/or gossypol treatments were not toxic at the doses and duration used in this study. These observations imply that gossypol and steroid hormones can interact to alter prostate development and gossypol metabolism and/or clearance.
Chang
W Y
WY
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Ohio State University, Columbus 43210, USA.
Shidaifat
F
F
Chang
C J
CJ
Kulp
S K
SK
Sugimoto
Y
Y
Canatan
H
H
Brueggemeier
R W
RW
Lin
Y C
YC
D058891:5-alpha Reductase Inhibitors; D000208:Acute Disease; D000818:Animals; D047072:Aromatase Inhibitors; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood / Q000633:toxicity*; D006072:Gossypol / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013737:Testis / Q000737:chemistry; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood / Q000633:toxicity*
D058891:5-alpha Reductase Inhibitors; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D013739:Testosterone; D004958:Estradiol; D006072:Gossypol