Premium
Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity
Author(s) -
Campos Silvana G. P.,
Gonçalves Bianca F.,
Scarano Wellerson R.,
Corradi Lara S.,
Santos Fernanda C. A.,
Custodio Ana M. G.,
Vilamaior Patricia S. L.,
Góes Rejane M.,
Taboga Sebastião R.
Publication year - 2010
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2010.00706.x
Subject(s) - flutamide , androgen , orchiectomy , apoptosis , prostate , hormone , castration , proliferating cell nuclear antigen , endocrinology , medicine , epithelium , androgen receptor , prostate cancer , blockade , andrology , biology , immunohistochemistry , receptor , cancer , pathology , biochemistry
Summary The present study examined the response of the prostate epithelium of senescent gerbils submitted to orchiectomy and with or without steroidal blockade. Animals were divided into five groups, all surgically castrated except the control group composed of intact animals. In the experimental groups, doses of flutamide and/or tamoxifen were applied for 1, 3, 7 and 30 days postcastration. The structural methods applied reveal that castration, whether associated or not with anti‐steroidal drugs, promoted short‐ and long‐term decrease in wet and relative weights of the prostate. The quantitative decline of epithelial compartment proportion observed at the end of treatment was due to the sum of slight changes in the epithelium and lumen. The apoptotic index had risen significantly at 1 day and declined at 7 days postcastration. Androgen receptor (AR) expression decreased after 3 days of hormonal ablation, coinciding with the highest levels of apoptosis and cell proliferation observed in all treated groups. The majority of cells remained differentiated in all groups due to CK 8/18 expression. Some animals remained with injuries such as carcinomas and adenocarcinomas after hormonal ablation. In the latter a mixture of AR‐positive and AR‐negative cells was identified. Microinvasive carcinomas found in the group treated for 30 days consisted of PCNA‐positive, inflammatory and non‐proliferating cells. Low apoptosis incidence and bcl‐2 positive cells were observed in these lesions. The treatments promoted a reduction of lesions in older gerbils, but treatment‐resistant tumours will improve understanding of the events that lead to hormone resistance.