Glucocorticoids (GCs) circulate in the plasma bound to corticosteroid-binding globulin (CBG). Plasma CBG may limit access of glucocorticoids to tissues (acting as a sponge: the free hormone hypothesis), or may solely serve as a transport molecule, releasing GCs to tissues as the plasma moves through capillaries (the total hormone hypothesis). Both biomedical (focused on human health) and comparative (focused on ecological and evolutionary relevance) studies have worked to incorporate CBG in glucocorticoid physiology, and to understand whether free or total hormone is the biologically active plasma fraction. The biomedical field, however, has been well ahead of the comparative physiologists, and have produced results that can inform comparative research when considering the import of total vs. free plasma hormone. In fact, biomedical studies have made impressive strides regarding the function of CBG in tissues as well as plasma; we, however, focus solely on the plasma functions in this review as this is the primary area of disagreement amongst comparative physiologists. Here we present 5 sets of biomedical studies across genomics, pharmacology, cell culture, whole animal research, and human medicine that strongly support a role for CBG limiting hormone access to tissue. We also discuss three areas of concern across comparative researchers. In contrast to former publications, we are not suggesting that all comparative studies in glucocorticoid physiology must measure CBG, or that only free corticosterone levels are valid. However, we propose that comparative physiologists be aware of biomedical results as they investigate glucocorticoids and interpret how total hormone may or may not impact behavior and physiology of free-living vertebrates.

糖皮质激素（GCs）在与皮质类固醇结合球蛋白（CBG）结合的血浆中循环。血浆CBG可能会限制糖皮质激素进入组织（充当海绵：游离激素假设），或仅充当转运分子，当血浆通过毛细血管移动时向组织释放GC（总激素假设）。生物医学研究（侧重于人类健康）和比较研究（侧重于生态和进化相关性）均已将CBG纳入糖皮质激素生理学，并了解游离激素或总激素是具有生物活性的血浆部分。然而，生物医学领域已经远远领先于比较生理学家，并且在考虑总血浆激素与游离血浆激素的进口量时所产生的结果可为比较研究提供参考。事实上，生物医学研究在组织和血浆中CBG的功能方面取得了令人瞩目的进步。但是，在本综述中，我们仅关注血浆功能，因为这是比较生理学家之间存在分歧的主要领域。在这里，我们介绍了5组生物医学研究，涉及基因组学，药理学，细胞培养，整个动物研究和人类医学，这些研究强烈支持CBG限制激素进入组织的作用。我们还将讨论比较研究人员关注的三个领域。与以前的出版物相比，我们并不建议所有糖皮质激素生理学的比较研究都必须测量CBG，或者仅游离皮质酮水平是有效的。然而，