Hampl R, Vondra K
Institute of Endocrinology, Prague, Czech Republic.
Physiol Res. 2017 Sep 26;66(Suppl 3):S295-S303. doi: 10.33549/physiolres.933725.
Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance. We have attempted to address following questions: 1) What does stay behind differences among patients as to their response to the (anti)steroid treatment? 2) Why do various tissues/cells respond differently to the same steroid hormone though they contain the same receptors? 3) Are such differences genetically dependent? The main attention was devoted to glucocorticoids as the most frequently used steroid therapeutics. Further, androgen insensitivity is discussed with a particular attention to acquired resistance to androgen deprivation therapy of prostate cancer. Finally the potential causes are outlined of breast and related cancer(s) resistance to antiestrogen therapy.
对类固醇激素产生耐药性是其在治疗中大规模使用时面临的一个严重问题。它可能由参与激素信号传导的基因突变在遗传上引起，这些基因不仅包括类固醇受体，还包括信号级联反应中的其他参与者，如共调节因子和其他核因子，它们介导激素产生的信号。另一种可能性是获得性耐药，它可能在长期类固醇治疗过程中出现，其中一种特殊情况是受体下调。在这篇综述中，总结了关于主要类固醇激素作用机制的最新知识，指出了已被证实或可能导致类固醇耐药的位点。我们试图回答以下问题：1）患者对（抗）类固醇治疗的反应存在差异的原因是什么？2）为什么各种组织/细胞虽然含有相同的受体，但对同一种类固醇激素的反应却不同？3）这些差异是否与遗传有关？主要关注的是作为最常用类固醇治疗药物的糖皮质激素。此外，还讨论了雄激素不敏感，特别关注前列腺癌对雄激素剥夺治疗的获得性耐药。最后，概述了乳腺癌及相关癌症对抗雌激素治疗耐药的潜在原因。
