In accordance with the present invention, there are provided methods for
modulating Phase II conjugating enzymes such as, for example, UGTs. Phase
II conjugating enzymes such as UGTs function in concert with Phase I
monooxygenase enzymes such as cytochrome P450 enzymes (CYPs) to eliminate
steroids and xenobiotics. Nuclear receptors SXR/PXR and CAR are
xenosensors regulating expression of CYP genes such as CYP3A and 2B. The
ability of this group of receptors to regulate expression of UGT in
response to steroids and/or xenobiotics provides novel approaches for
direct regulation/activation of a glucuronidation pathway, thereby
providing methods to achieve physiologic homeostasis with respect to
steroids and/or xenobiotics. SXR/PXR and CAR regulation/activation of UGT
represents the first evidence of receptors that can
transduce/transactivate both Phase I and Phase II adaptive hepatic
response. In another aspect, the present invention also provides
transgenic rodents expressing one or more of SXR, CAR or PXR.