And these rules are: One. Proteins like to change shape when stuff binds to them. And two. Changing shapes can allow proteins to bind or unbind with other stuff.
Glucocorticoids are not soluble in water, so most cortisol in the blood is bound to a special carrier protein, called cortisol-binding globulin, and only about 5% is unbound or free.
We might go through one in a plane crossing the icefields of northern Canada or at 3am, alone in a foreign hotel bedroom, contemplating matters from a new unbound perspective.