Structural and Cell Biology Program, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
Department of Morphology, Institute of Biosciences, UNESP - Univ Estadual Paulista, Botucatu, SP, Brazil.
Life Sci. 2015 Jan 1;120:22-30. doi: 10.1016/j.lfs.2014.11.003. Epub 2014 Nov 14.
Chronic ethanol consumption leads to reproductive damages, since it can act directly in the tissues or indirectly, causing a hormonal imbalance. Prostate is a hormone-dependent gland and, consequently, susceptible to ethanol. The potential of testosterone therapy in the ethanol-related disorders was investigated in the prostate microenvironment.
UChB rats aged 90 days were divided into 2 experimental groups (n=20): C: drinking water only and EtOH: drinking 10% (v/v) ethanol at >2 g/kg body weight/day+water. At 150 days old, 10 rats from each group received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks, constituting T and EtOH+T, while the remaining animals received corn oil as vehicle. Animals were euthanized at 180 days old, by decapitation. Blood was collected to obtain hormone concentrations and ventral prostate was dissected and processed for light microscope and molecular analyses.
Ventral prostate weight, plasma testosterone and DHT and intraprostatic testosterone concentrations were increased after testosterone treatment. Plasma estradiol level was reduced in the EtOH+T. Inflammatory foci, metaplasia and epithelial atrophy were constantly found in the prostate of EtOH and were not observed after hormonal therapy. No differences were found in the expression of AR, ERβ and DACH-1. Additionally, testosterone treatment down-regulated ERα and increased the e-cadherin and α-actinin immunoreactivities.
Testosterone was able to reverse damages caused by ethanol consumption in the prostate microenvironment and becomes a possible target to be investigated to ethanol-related disorders.
慢性乙醇摄入会导致生殖系统损伤,因为它既能直接作用于组织,也能通过造成激素失衡而间接地产生影响。前列腺是一种依赖于激素的腺体,因此容易受到乙醇的影响。本研究旨在探究在前列腺微环境中,睾酮治疗是否对乙醇相关疾病有潜在作用。
90 天大的 UChB 大鼠被分为 2 个实验组(n=20):C 组:仅饮用去离子水;EtOH 组:饮用 10%(v/v)乙醇,超过 2g/kg 体重/天+去离子水。150 天时,每组 10 只大鼠接受经皮注射睾酮环戊丙酸酯(5mg/kg 体重),溶于玉米油中,每两天一次,共 4 周,构成 T 和 EtOH+T 组,而其余动物则接受玉米油作为载体。180 天时,大鼠通过断头处死,采集血液以获得激素浓度,并解剖分离腹侧前列腺,进行光镜和分子分析。
睾酮处理后,腹侧前列腺重量、血浆睾酮和二氢睾酮以及前列腺内睾酮浓度增加。EtOH+T 组的血浆雌二醇水平降低。乙醇组的前列腺中始终存在炎症灶、化生和上皮萎缩,但在激素治疗后这些现象均未观察到。AR、ERβ和 DACH-1 的表达无差异。此外,睾酮治疗下调了 ERα,增加了 E-钙黏蛋白和α-辅肌动蛋白的免疫反应性。
睾酮能够逆转乙醇摄入对前列腺微环境造成的损伤,可能成为治疗与乙醇相关疾病的潜在靶点。