Plasma protein-mediated transport of steroid and thyroid hormones

Abstract

The free hormone or free drug hypotheses have traditionally assumed that the concentration of cellular exchangeable hormone (i.e., the pool that drives cellular hormone or drug receptor occupancy) can be reliably estimated by in vitro measurements of unbound hormone concentrations. The corollary of this view is that the large reservoir of bound hormone in blood is passively transported by plasma proteins and is physiologically inactive. However, when these assumptions are subjected to direct empiric testing with either in vivo or perfused organ techniques, it is found that the large pool of bound hormone in blood is operationally available for transport across microcirculatory barriers without the plasma protein, per se, significantly exiting the plasma compartment. This process is believed to involve a mechanism of enhanced dissociation of hormone or drug from the plasma protein caused by transient conformational changes about the ligand binding site within the microcirculation: The biochemical mechanism of the interaction of the plasma protein with the surface of the microcirculation may involve receptor, charged selectivity, or local inhibitor mechanisms.