Division of Endocrinology and Metabolism, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Steroids. 2011 Aug;76(9):822-8. doi: 10.1016/j.steroids.2011.02.016. Epub 2011 Feb 25.
Steroids are key factors in a myriad of mammalian biological systems, including the brain, kidney, heart, bones, and gonads. While alternative potential steroid receptors have been described, the majority of biologically relevant steroid responses appear to be mediated by classical steroid receptors that are located in all parts of the cell, from the plasma membrane to the nucleus. Interestingly, these classical steroid receptors modulate different signals depending upon their location. For example, receptors in the plasma membrane interact with membrane signaling molecules, including G proteins and kinases. In contrast, receptors in the nucleus interact with nuclear signaling molecules, including transcriptional co-regulators. These extranuclear and intranuclear signals function together in an integrated fashion to regulate important biological functions. While most studies on extranuclear steroid signaling have focused on estrogens, recent work has demonstrated that nongenomic androgen signaling is equally important and that these two steroids modulate similar signaling pathways. In fact, by taking advantage of a simple model system whereby a physiologically relevant androgen-mediated process is regulated completely independent of transcription (Xenopus laevis oocyte maturation), many novel and conserved concepts in nongenomic steroid signaling have been uncovered and characterized.
甾体激素是哺乳动物众多生物系统的关键因素,包括大脑、肾脏、心脏、骨骼和性腺。虽然已经描述了其他潜在的甾体激素受体,但大多数有生物学意义的甾体激素反应似乎都是由位于细胞各个部位(从细胞膜到细胞核)的经典甾体激素受体介导的。有趣的是,这些经典甾体激素受体根据其位置调节不同的信号。例如,细胞膜上的受体与膜信号分子(包括 G 蛋白和激酶)相互作用。相比之下,核内受体与核信号分子(包括转录共调节剂)相互作用。这些核外和核内信号共同以整合的方式发挥作用,调节重要的生物学功能。虽然大多数关于核外甾体激素信号的研究都集中在雌激素上,但最近的研究表明,非基因组雄激素信号同样重要,并且这两种甾体激素调节相似的信号通路。事实上,通过利用一种简单的模型系统,其中一种生理相关的雄激素介导的过程完全独立于转录(非洲爪蟾卵母细胞成熟)进行调节,许多新的和保守的非基因组甾体激素信号转导概念已经被揭示和描述。