Biphasic entry of glucocorticoids into cultured human skin keratinocytes and fibroblasts.

The uptake of glucocorticoids by cultured human skin keratinocytes and fibroblasts was found to be a rapid, temperature-sensitive process. All glucocorticoids tested accumulated in the cells, and the ratio between the intracellular and extracellular concentrations (ci/co ratio) was higher than 1. For most of the glucocorticoids under study there was good correlation between the lipophilicity and the rate of uptake. Since the uptake of glucocorticoids seems to be unsaturable in the concentration range used and no competition was observed between these compounds for entry into the cells, it may be assumed that the uptake of glucocorticoids is essentially a simple diffusion process based on a distribution of glucocorticoids between a lipid-rich phase and water. The analysis of the uptake process revealed that the entry of glucocorticoids into cultured human skin fibroblasts and keratinocytes is a non-mediated passive diffusion process that involves two distinct steps: a rapid, non-specific, high-capacity association to the cell membrane followed by a slower internalization process associated with a stronger binding of glucocorticoids within the cell.