Mechanisms by which expression of a single gene is regulated can be extremely complicated. Multiple phosphorylation-or ligand-dependent nuclear receptors that homo-or heterodimerize may be required to achieve activity. Each of these receptors may have different activation specificity or duration, even when acting via the same regulatory DNA sequence such as classical proximal promoter elements. These receptors may also work in combination with other transcription factors that function at sites more distal from the proximal promoter or in introns. Alternatively spliced transcripts represent another complex aspect of gene expression regulation that is influenced by extracellular and intracellular signaling but is not well understood (Stamm et al. 2005) . Furthermore, individual genes often are part of a broader, coordinately regulated network of genes that function to elicit a set of cellular responses (Wagner 1999) . Through such mechanisms, ligands may, for instance, induce their own metabolism or export, a process that further complicates understanding of gene regulation and that also has critical implications for models of pharmacokinetics and drug efficacy.