Protein profiling of rat ventral prostate following chronic finasteride administration: identification and localization of a novel putative androgen-regulated protein.
To better understand the effects of antiandrogens on the prostate, we investigated the changes in the proteome of rat ventral prostate (VP) following treatment with a well characterized 5alpha-reductase inhibitor, finasteride. Sprague-Dawley rats were treated daily by gavage with finasteride at 0, 1, 5, 25, and 125 mg/kg/day. Changes in plasma hormone levels as well as the weight and histology of sex accessory tissues were determined after 28 days of treatment and showed a dose-related decrease of VP weights together with a marked atrophy of the tissue visible at the macroscopic and microscopic levels. In addition, significant reductions in seminal vesicle and epididymis weights were noted. VP proteins were analyzed by two-dimensional gel electrophoresis: 37 proteins, mainly involved in protein synthesis, processing, and cellular trafficking and in metabolism, detoxification, and oxidative stress, were identified as modulated by finasteride. The prominent feature of this study is the demonstration of finasteride dose-dependent up-regulation of a protein similar to l-amino-acid oxidase 1 (Lao1). An up-regulation of this protein was also observed with the antiandrogen flutamide. Lao1 expression occurred as early as 48 h after antiandrogen administration and persisted throughout the treatment duration. Immunohistochemistry showed that this protein was only detectable in epithelial cells and secretory vesicles. Altogether these data point to a potential use of Lao1 to reveal antiandrogen-induced prostate injury.
Cayatte
Corinne
C
INSERM U638, Nice, France.
Pons
Catherine
C
Guigonis
Jean-Marie
JM
Pizzol
Jérôme
J
Elies
Laetitia
L
Kennel
Philippe
P
Rouquié
David
D
Bars
Rémi
R
Rossi
Bernard
B
Samson
Michel
M
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004847:Epithelial Cells / Q000201:enzymology; D018120:Finasteride / Q000008:administration & dosage*; D050830:L-Amino Acid Oxidase / Q000032:analysis / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D040081:Protein Array Analysis; D011506:Proteins / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D011506:Proteins; D014443:Tyrosine; D018120:Finasteride; D050830:L-Amino Acid Oxidase