The vast majority of glucocorticoid activity in most mammals is from cortisol, also known as hydrocortisone. Corticosterone, the major glucocorticoid in rodents, is another glucocorticoid.
Cortisol binds to the glucocorticoid receptor in the cytoplasm and the hormone-receptor complex is then translocated into the nucleus, where it binds to its DNA response element and modulates transcription from a battery of genes, leading to changes in the cell's phenotype.
Only about 10% of circulating cortisol is free. The remaining majority circulates bound to plasma proteins, particularly corticosteroid-binding globulin (transcortin). This protein binding likely decreases the metabolic clearance rate of glucocorticoids and, because the bound steroid is not biologically active, tends to act as a buffer and blunt wild fluctuations in cortisol concentration.