The interconversion of prednisone and prednisolone in human and rabbit organs in vitro is a function of tissue...

The interconversion and elimination of prednisone (PO) and prednisolone (POH) were examined in human and rabbit liver, kidney, lung and skeletal muscle preparations to determine the effect of organ disruption on in vitro metabolism within multiple organs of two species. Results from microsomes, homogenates and minces were compared to determine the effect of various stages of tissue disruption on the reversible and irreversible metabolism of the glucocorticoids. Oxidation of POH to PO was enhanced by homogenization of all the organs examined; further disruption by subcellular fractionation to microsomes reduced oxidation relative to homogenates but yielded values greater than the original minces. The reverse reaction, reduction of PO to POH, was also enhanced by homogenization, but microsomal preparations were less active than the minces. The irreversible elimination of the glucocorticoids was progressively diminished by disruption of normal architecture in all organs. Results of in vitro studies of glucocorticoid metabolism have provided discrepant results, as a function of the laboratory, the species, the organ and the organ preparation examined. These results provide insights into the source of discrepant results regarding steroid metabolism, as it appears that results of experimentation with glucocorticoid conversion and/or elimination may be a function of the method used. Additionally, the data support the hypothesis that the enzyme system involved in the interconversion of the glucocorticoids may not be a simple single protein which acts bidirectionally.