Role of UDP-glucuronosyltransferases (UGT) in steroid metabolism

The mechanism of conjugation of various compounds by glucuronidation has be en described in all vertebrates studied to date. Uridine diphospho-glucuron osyltransferase (UGT) are membrane-bound enzymes localized in the endoplasm ic reticulum of most of human cells, where they catalyze the transfer of th e glucuronyl group from uridine 5'-diphosphoglucuronic to active endogenous and exogenous molecules bearing functional groups of oxygen, nitrogen, sul fur and carbon. The resulting glucuronide products are generally hydrosolub le, more polar, less toxic and more easily excreted than the substrate mole cule. Examples of such substrates include bilirubin, bile acids and steroid s, although xenobiotics such as drugs and pollutants are also detoxified by UGT enzymes. Under normal physiological conditions, the glucuronidation re action is irreversible, thereby leading to the inactivation and catabolism of several molecules, including steroid hormones. UGTs are important enzyme s involved in the regulation of intracellular steroid concentrations and, t herefore, in the control of the hormonal response.