Effect of Testosterone on Proliferation Markers and Apoptosis in Breasts of Ovariectomized Rats

Abstract Objective To investigate the action of testosterone (T), isolated or associated with estradiol benzoate (EB), on the proliferation markers and apoptosis of breasts of ovariectomized rats. Methods A total of 48 castrated female Wistar rats were divided into 6 groups, and each of them were submitted to one of the following treatments for 5 weeks: 1) control; 2) EB 50 mcg/day + T 50 mcg/day; 3) T 50mcg/day; 4) EB 50 mcg +T 300 mcg/day; 5) T 300 mcg/day; and 6) EB 50 mcg/day. After the treatment, the mammary tissue was submitted to a histological analysis and immunoexpression evaluation of proliferation markers (proliferating cell nuclear antigen, PCNA) and apoptosis (caspase-3). Results There was a statistically significant difference among the groups regarding microcalcifications and secretory activity, with higher prevalence in the groups treated with EB. There was no difference among the groups regarding atrophy, but a higher prevalence of atrophy was found in the groups that received T versus those that received EB +T. There was a difference among the groups regarding the PCNA (p = 0.028), with higher expression in the group submitted to EB +T 300 mcg/day. Regarding caspase-3, there was no difference among the groups; however, in the group submitted to EB +T 300 mcg/day, the expression was higher than in the isolated T group. Conclusion Isolated T did not have a proliferative effect on the mammary tissue, contrary to EB. Testosterone in combination with EB may or may not decrease the proliferation, depending on the dose of T.

摘要 目的：探讨单独或联合苯甲酸雌二醇（Estradiol Benzoate, EB）的睾酮（Testosterone, T）对去卵巢大鼠乳腺组织增殖标志物及细胞凋亡的影响。方法：共纳入48只去势雌性Wistar大鼠，随机分为6组，每组分别接受以下一种处理方案，持续5周：1）对照组；2）苯甲酸雌二醇（EB）50 μg/天+睾酮（T）50 μg/天；3）睾酮（T）50 μg/天；4）苯甲酸雌二醇（EB）50 μg+睾酮（T）300 μg/天；5）睾酮（T）300 μg/天；6）苯甲酸雌二醇（EB）50 μg/天。处理结束后，对乳腺组织进行组织学分析，并检测增殖标志物（增殖细胞核抗原（proliferating cell nuclear antigen, PCNA））与细胞凋亡（半胱氨酸天冬氨酸蛋白酶3（caspase-3））的免疫表达水平。结果：各组在乳腺微钙化与分泌活性方面存在统计学显著性差异，苯甲酸雌二醇（EB）处理组的微钙化与分泌活性发生率更高。各组在乳腺萎缩方面无显著差异，但接受睾酮（T）处理的大鼠组萎缩发生率高于联合使用苯甲酸雌二醇与睾酮（EB+T）的组。各组的增殖细胞核抗原（PCNA）表达水平存在显著差异（p=0.028），其中苯甲酸雌二醇（EB）50 μg+睾酮（T）300 μg/天处理组的PCNA表达水平更高。关于半胱氨酸天冬氨酸蛋白酶3（caspase-3）的表达，各组总体无显著差异，但苯甲酸雌二醇（EB）50 μg+睾酮（T）300 μg/天处理组的表达水平高于单独使用睾酮（T）的组。结论：单独使用睾酮（T）对乳腺组织无增殖作用，与苯甲酸雌二醇（EB）的作用相反。睾酮与苯甲酸雌二醇联合使用时，是否会抑制乳腺组织增殖取决于睾酮的给药剂量。