RGD Reference Report - Ethynylestradiol increases expression and activity of rat liver MRP3. - Rat Genome Database

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Ethynylestradiol increases expression and activity of rat liver MRP3.

Authors: Ruiz, ML  Villanueva, SS  Luquita, MG  Vore, M  Mottino, AD  Catania, VA 
Citation: Ruiz ML, etal., Drug Metab Dispos. 2006 Jun;34(6):1030-4. Epub 2006 Mar 22.
RGD ID: 2301068
Pubmed: PMID:16554369   (View Abstract at PubMed)
DOI: DOI:10.1124/dmd.106.009316   (Journal Full-text)

We evaluated the effect of ethynylestradiol (EE) administration (5 mg/kg b.wt. s.c., for 5 consecutive days) on the expression and activity of multidrug resistance-associated protein 3 (Mrp3) in rats. Western blotting analysis revealed decreased Mrp2 (-41%) and increased Mrp3 (+200%) expression by EE. To determine the functional impact of up-regulation of Mrp3 versus Mrp2, we measured the excretion of acetaminophen glucuronide (APAP-glu), a common substrate for both transporters, into bile and perfusate in the recirculating isolated perfused liver (IPL) model. APAP-glu was generated endogenously from acetaminophen (APAP), which was administered as a tracer dose (2 micromol/ml) into the perfusate. Biliary excretion of APAP-glu after 60 min of perfusion was reduced in EE-treated rats (-80%). In contrast, excretion into the perfusate was increased by EE (+45%). Liver content of APAP-glu at the end of the experiment was reduced by 36% in the EE group. The total amount of glucuronide remained the same in both groups. Taken together, these results indicate that up-regulation of Mrp3 led to an exacerbated basolateral versus canalicular excretion of conjugated APAP in IPL. We conclude that induced expression of basolateral Mrp3 by EE may represent a compensatory mechanism to prevent intracellular accumulation of common Mrp substrates, either endogenous or exogenous, due to reduced expression and activity of apical Mrp2.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to estradiol  IEP 2301068 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc3  (ATP binding cassette subfamily C member 3)


Additional Information