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Hormonal Regulation of Hepatic Drug Biotransformation and Transport Systems

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The human body is constantly exposed to many xenobiotics including environmental pollutants, food additives, therapeutic drugs, etc. The liver is considered the primary site for drug metabolism and elimination pathways, consisting in uptake, phase I and II reactions, and efflux processes, usually acting in this same order. Modulation of biotransformation and disposition of drugs of clinical application has important therapeutic and toxicological implications. We here provide a compilation and analysis of relevant, more recent literature reporting hormonal regulation of hepatic drug biotransformation and transport systems. We provide additional information on the effect of hormones that tentatively explain differences between sexes. A brief discussion on discrepancies between experimental models and species, as well as a link between gender‐related differences and the hormonal mechanism explaining such differences, is also presented. Finally, we include a comment on the pathophysiological, toxicological, and pharmacological relevance of these regulations. © 2013 American Physiological Society. Compr Physiol 3:1721‐1740, 2013.

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Figure 1. Figure 1. Processing of endo‐ and xenobiotics in the hepatocytes. X: Endo‐ or xenobiotic. U: Uptake transporters such as NTCP, OATs, or OATPs. After uptake from the bloodstream, endo‐ and xenobiotics are metabolized by Phase I (CYP450 family) and/or Phase II (UGT, GST, and/or SULT). M: final metabolite. Metabolites are then eliminated from the cells through secretion into bile canaliculi or into sinusoids by efflux transporters (E) such as MRP2, BSEP, BCRP, P‐GP, and ABCG5/8 (canalicular) or MRP3‐4‐5‐6 (basolateral).

Figure 1. Processing of endo‐ and xenobiotics in the hepatocytes. X: Endo‐ or xenobiotic. U: Uptake transporters such as NTCP, OATs, or OATPs. After uptake from the bloodstream, endo‐ and xenobiotics are metabolized by Phase I (CYP450 family) and/or Phase II (UGT, GST, and/or SULT). M: final metabolite. Metabolites are then eliminated from the cells through secretion into bile canaliculi or into sinusoids by efflux transporters (E) such as MRP2, BSEP, BCRP, P‐GP, and ABCG5/8 (canalicular) or MRP3‐4‐5‐6 (basolateral).
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María L. Ruiz, Aldo D. Mottino, Viviana A. Catania, Mary Vore. Hormonal Regulation of Hepatic Drug Biotransformation and Transport Systems. Compr Physiol 2013, 3: 1721-1740. doi: 10.1002/cphy.c130018