Department of Endocrinology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
Biomed Res Int. 2013;2013:407678. doi: 10.1155/2013/407678. Epub 2013 Sep 17.
To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR) and connexin 43 (Cx43) in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20), neonatal (PD2), and prepubertal (PD90) exposure to an antiandrogen flutamide (50 mg/kg bw). In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages.
迄今为止,人们对于雄激素信号在调控成年前列腺中雄激素受体 (AR) 和连接蛋白 43 (Cx43) 的特定发育时期的作用所知甚少。因此,在这项研究中,我们检测了暴露于抗雄激素氟他胺(50mg/kg bw)后的胎儿期(GD20)、新生期(PD2)和青春期前(PD90)公猪前列腺中 AR 和 Cx43 的 mRNA 和蛋白表达以及组织分布。在 GD20 和 PD2 雄性动物中,我们发现腔室减少、炎症改变、AR 减少和 Cx43 表达增加,以及两种蛋白的定位改变。此外,这些动物的前列腺中检测到凋亡增强和增殖减少。在 PD90 雄性动物中,这些改变不太明显,但 Cx43 的表达明显上调。本文的研究结果表明,在公猪中,早期胎儿和新生儿期的雄激素作用对于维持成年前列腺细胞的正常表型和功能起着关键作用。此外,我们证明了前列腺中 Cx43 表达的调节可以作为不同发育阶段激素干扰的敏感标志物。