STEROID UDP GLUCURONOSYLTRANSFERASES - CHARACTERIZATION AND REGULATION

Under normal physiological conditions, glucuronidation generally termi nates the biological activities of steroids and leads to their elimina tion in the bile and urine. This process is postulated to play a role in homeostasis by regulating the intracellular steady-state levels of these effector ligands. Indeed, the duration of response to specific s teroid signals may be partly determined by the capacity of the cell or tissue to eliminate the steroids as unreactive glucuronides. Under pa thophysiological conditions or during steroid therapies, glucuronidati on may sometimes result in the formation of more biologically active o r toxic metabolites as exemplified by the steroid D ring glucuronides. The degree of toxicity or biological effect in the cell exposed to th ese steroids will also depend on its complement of UGTs. To investigat e these processes in more detail, the steroid specificities and distri bution of individual UGTs in various target organs require elucidation In this review, our current knowlege of the steroid specificities of various rat and human UGTs is described and preliminary investigations on the mechanisms governing tissue specificity are presented.