Figure 4.

Theoretical comparison of circulating and tissue steroid concentrations. (A) If the same amounts of steroid are present in equal volumes of blood and brain, different interpretations can be made, depending on how steroids are quantified in blood. In the circulation, the vast majority of corticosterone is bound to corticosteroid-binding globulin (CBG; Hammond, 1990). CBG-bound steroids have very limited access to tissue and limited ability to cross the blood–brain barrier. (B) Corticosterone concentrations in whole blood are approximately 50% of those in plasma (Taves et al., 2010), and within plasma, the vast majority of corticosterone is bound to CBG. In the above theoretical scenario, if whole blood corticosterone is measured, then circulating levels appear identical to tissue levels. If plasma total corticosterone is measured, then circulating levels appear much higher than tissue levels. If plasma free corticosterone is measured, then circulating levels appear much lower than tissue levels. Thus, the use of whole blood steroid measurements or plasma free steroid measurements is highly informative in addition to plasma total steroid measurements.