Testosterone transport in brain: primary role of plasma protein-bound hormone

Physiologically based mathematical modeling is used to predict the steady-state concentration of intracellular free and bound testosterone in brain. On the basis of previous in vivo tracer kinetic studies of blood-to-brain and brain-to-blood transport of testosterone in the rat, values are assigned to various physiological parameters (hormone association and dissociation reactions with plasma and cytosolic binding proteins, capillary transit time, and membrane transport). The model does not adhere to the restrictions of the free hormone hypothesis and allows for the enhanced transport of hormone from the plasma protein-bound pool into the tissue extravascular space. This process is believed to occur via an endothelial inhibition of ligand binding to the plasma protein without the protein crossing the endothelial wall. The model predicts that the steady-state concentration of intracellular free hormone changes in parallel more closely to changes in the concentration of plasma protein-bound hormone as measured in vitro and not the free hormone as measured in vitro.