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.

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循环中睾酮结合的重新评估：生理和临床意义


在循环中，睾酮和其他性激素与结合蛋白结合，在调节其运输、分布、代谢和生物活性方面发挥着重要作用。根据已被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，准确确定睾酮在结合部分和游离部分之间的分配对于我们理解睾酮向靶组织的递送和生物活性如何调节以及因此对男性和女性雄激素紊乱的诊断和治疗至关重要。在这里，我们从历史角度展示了我们对睾酮与循环结合蛋白结合的理解的演变。在对文献和实验数据进行评估的基础上，我们表明，睾酮与性激素结合球蛋白和人血清白蛋白结合的主流模型的化学计量、结合动力学和亲和力的假设不受以下支持：已发表的实验数据很可能不准确。本综述为游离睾酮测量在雄激素紊乱患者的诊断和治疗中的应用提供了一些指导原则。睾酮处方数量的不断增加以及直接测量和游离睾酮浓度计算的广泛认可的问题使得这一批判性审查变得及时且具有临床相关性。