Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Mol Cell Endocrinol. 2018 Apr 15;465:4-26. doi: 10.1016/j.mce.2017.08.016. Epub 2017 Sep 1.
Androgens play an important role in metabolic homeostasis and reproductive health in both men and women. Androgen signalling is dependent on androgen receptor activation, mostly by testosterone and 5α-dihydrotestosterone. However, the intracellular or intracrine activation of C androgen precursors to active androgens in peripheral target tissues of androgen action is of equal importance. Intracrine androgen synthesis is often not reflected by circulating androgens but rather by androgen metabolites and conjugates. In this review we provide an overview of human C steroid biosynthesis including the production of 11-oxygenated androgens, their transport in circulation and uptake into peripheral tissues. We conceptualise the mechanisms of intracrinology and review the intracrine pathways of activation and inactivation in selected human tissues. The contribution of liver and kidney as organs driving androgen inactivation and renal excretion are also highlighted. Finally, the importance of quantifying androgen metabolites and conjugates to assess intracrine androgen production is discussed.
雄激素在男性和女性的代谢稳态和生殖健康中都起着重要作用。雄激素信号依赖于雄激素受体的激活，主要由睾酮和 5α-二氢睾酮介导。然而，在雄激素作用的外周靶组织中，C 雄激素前体的细胞内或胞内激活转化为活性雄激素同样重要。细胞内雄激素合成通常不能反映循环雄激素，而是反映雄激素代谢物和缀合物。在这篇综述中，我们概述了人类 C 类固醇生物合成，包括 11-氧代雄激素的产生、它们在循环中的运输以及进入外周组织的摄取。我们将胞内科学的机制概念化，并回顾了选定人体组织中激活和失活的胞内途径。肝脏和肾脏作为驱动雄激素失活和肾脏排泄的器官的作用也得到了强调。最后，讨论了定量雄激素代谢物和缀合物以评估细胞内雄激素生成的重要性。
