Laboratório de Endocrinologia Experimental e Eletrofisiologia, Departamento de Fisiologia, PPG Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, Sala 337, Porto Alegre, RS, Brazil.
Centro Universitário Ritter dos Reis, UNIRITTER, Porto Alegre, RS, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Porto Alegre, RS, Brazil.
Mol Cell Endocrinol. 2018 Feb 5;461:112-121. doi: 10.1016/j.mce.2017.08.023. Epub 2017 Sep 1.
Epitestosterone is the 17α-epimer of testosterone and has been described as an anti-androgen, since it inhibits the effects produced by testosterone and dihydrotestosterone via the nuclear androgen receptor (nAR). However, epitestosterone also displays an effect which is similar to the non-classical effect of testosterone, depolarizing the membrane potential of Sertoli cells and inducing a rapid Ca uptake. This study aimed to investigate the effects of a treatment with epitestosterone on developmental parameters of immature rats. Animals were chemically castrated by using the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix and then received a replacement of 7 days with epitestosterone or testosterone. Replacement with either epitestosterone or testosterone restored the anogenital distance (AGD) and testicular weight which had been reduced by chemical castration. The immunocontent of nAR and the nAR-immunoreactivity were reduced by epitestosterone treatment in the testis of both castrated and non-castrated animals. Furthermore, testosterone was unable of changing the membrane potential of Sertoli cells through its non-classical action in the group of animals castrated and replaced with epitestosterone. In conclusion, in relation to the level of protein expression of nAR epitestosterone acts as an anti-androgen. However, it acts in the same way as testosterone when genital development parameters are evaluated. Moreover, in castrated rats epitestosterone suppressed the non-classical response of testosterone, changing the pattern of testosterone signalling via a membrane mechanism in Sertoli cells.
表雄酮是睾酮的 17α-差向异构体，已被描述为一种抗雄激素，因为它通过核雄激素受体 (nAR) 抑制睾酮和二氢睾酮产生的作用。然而，表雄酮还表现出类似于睾酮的非经典作用的效果，去极化支持细胞的膜电位并诱导快速 Ca 摄取。本研究旨在研究用表雄酮处理对未成熟大鼠发育参数的影响。动物通过使用促性腺激素释放激素 (GnRH) 拮抗剂 cetrorelix 进行化学去势，然后用表雄酮或睾酮替代 7 天。用表雄酮或睾酮替代均可恢复因化学去势而降低的肛生殖器距离 (AGD) 和睾丸重量。在去势和未去势动物的睾丸中，表雄酮处理降低了 nAR 的免疫含量和 nAR 免疫反应性。此外，在与表雄酮一起去势和替代的动物组中，睾酮无法通过其非经典作用改变支持细胞的膜电位。总之，就 nAR 的蛋白表达水平而言，表雄酮作为一种抗雄激素。然而，当评估生殖发育参数时，它的作用与睾酮相同。此外，在去势大鼠中，表雄酮抑制了睾酮的非经典反应，通过支持细胞中的膜机制改变了睾酮信号转导的模式。
