Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Andrology Research Unit, Centre for Endocrinology and Diabetes, University of Manchester, Manchester M13 9PT, United Kingdom.
Endocr Rev. 2017 Aug 1;38(4):302-324. doi: 10.1210/er.2017-00025.
In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.
在循环中，睾酮和其他性激素与结合蛋白结合，这些结合蛋白在调节它们的运输、分布、代谢和生物活性方面发挥着重要作用。根据广泛争论的游离激素假说，只有未结合或游离的部分在靶组织中具有生物活性。因此，准确测定睾酮在结合和游离部分之间的分配对于我们理解其向靶组织的输送以及生物活性如何受到调节至关重要，从而也有助于男性和女性雄激素紊乱的诊断和治疗。在这里，我们回顾了我们对睾酮与循环结合蛋白结合的理解的演变。在评估文献和实验数据的基础上，我们表明，目前关于睾酮与性激素结合球蛋白和人血清白蛋白结合的模型的化学计量学、结合动力学和亲和力的假设，并没有得到已发表的实验数据的支持，而且很可能是不准确的。这篇综述为雄激素紊乱患者的诊断和治疗中应用游离睾酮测量提供了一些指导原则。越来越多的睾酮处方以及直接测量和计算游离睾酮浓度中广泛认识到的问题，使得这篇批判性综述具有及时性和临床相关性。
