The first isolation and structure identifications of prednisone and prednisolone were done in 1950 by Arthur Nobile .    The first commercially feasible synthesis of prednisone was carried out in 1955 in the laboratories of Schering Corporation, which later became Schering-Plough Corporation , by Arthur Nobile and coworkers.  They discovered that cortisone could be microbiologically oxidized to prednisone by the bacterium Corynebacterium simplex. The same process was used to prepare prednisolone from hydrocortisone . 
As a glucocorticoid , the lipophilic structure of prednisolone allows for easy passage through the cell membrane where it then binds to its respective glucocorticoid receptor (GCR) located in the cytoplasm. Upon binding, formation of the GC/GCR complex causes dissociation of chaperone proteins from the glucocorticoid receptor enabling the GC/GCR complex to translocate inside the nucleus. This process occurs within 20 minutes of binding. Once inside the nucleus, the homodimer GC/GCR complex binds to specific DNA binding-sites known as glucocorticoid response elements (GREs) resulting in gene expression or inhibition. Complex binding to positive GREs leads to synthesis of anti-inflammatory proteins while binding to negative GREs block the transcription of inflammatory genes.