title: Comparison of histological compositions and apoptosis in canine spontaneous benign prostatic hyperplasia treated with androgen suppressive agents chlormadinone acetate and finasteride.
abstract: OBJECTIVE
  Chlormadinone acetate and finasteride are androgen suppressive agents clinically used for benign prostatic hyperplasia but their mechanism for inducing prostatic atrophy differs. We investigated the effect of these androgen suppressive agents on prostatic histology and apoptosis using the spontaneous canine benign prostatic hyperplasia model.
  
  
  METHODS
  Animals were treated with oral chlormadinone acetate or finasteride for 25 weeks. The prostatic volumes were analyzed every 5 weeks. Prostatic androgen and estrogen concentrations, histological composition and apoptosis were determined at the end of treatment. Apoptosis was measured by in situ labeling of 3' hydroxy ends of the DNA breaks using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method.
  
  
  RESULTS
  There was a similar volume reduction effect with 0.3 mg./kg. chlormadinone acetate daily and 1 mg./kg. finasteride daily. Chlormadinone acetate decreased testosterone and dihydrotestosterone but finasteride decreased only dihydrotestosterone in the prostate gland. The concentration ratio of estradiol-to-total androgen in the prostate was significantly increased in finasteride treated canines. Chlormadinone acetate and finasteride decreased the epithelial and stromal components. The extent of apoptosis observed in the prostate was significantly higher in the chlormadinone acetate group compared to that of the control and finasteride groups.
  
  
  CONCLUSIONS
  Although a similar effect of chlormadinone acetate and finasteride was observed in the induction of prostatic regression and composition of the histological components, the sustained increase in apoptosis was observed only in chlormadinone acetate treated canines. We suggest that different intraprostatic endocrine environments created by chlormadinone acetate or finasteride, which have different intraprostatic testosterone levels and estradiol-to-androgen ratios, may be responsible for the different outcomes in the extent of apoptosis.
authors: Department of Urology, Gunma University School of Medicine, Maebashi, Japan.
authors: Y
authors: Y
authors: Shibata
authors: Y
authors: Y
authors: Fukabori
authors: K
authors: K
authors: Ito
authors: K
authors: K
authors: Suzuki
authors: H
authors: H
authors: Yamanaka
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002715:Chlormadinone Acetate / Q000627:therapeutic use*; D013196:Dihydrotestosterone / Q000378:metabolism; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004958:Estradiol / Q000378:metabolism; D018120:Finasteride / Q000627:therapeutic use*; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary; D013739:Testosterone / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D013196:Dihydrotestosterone; D002715:Chlormadinone Acetate; D013739:Testosterone; D004958:Estradiol; D018120:Finasteride