Effect of glucocorticoids on regulation of placental multidrug resistance phosphoglycoprotein (P-gp) in the mouse

Placenta
Sophie PetropoulosS G Matthews

Abstract

Previously, we and others have shown that placental Abcb1 mRNA and phosphoglycoprotein (P-gp; encoded by Abcb1 mRNA) decreases over the second half of gestation, resulting in increased accumulation of P-gp substrates in the fetal compartment. Very little is known pertaining to the regulation of placental Abcb1 mRNA and P-gp. In non-placental adult murine tissues, synthetic glucocorticoids have been shown to regulate Abcb1 (Abcb1a and Abcb1b) mRNA in an isoform and tissue-specific manner. Furthermore, given that maternal and fetal endogenous glucocorticoid levels increase dramatically in late gestation, we hypothesized that synthetic glucocorticoids down-regulate placental Abcb1 and P-gp expression, consequently decreasing placental P-gp mediated fetal protection. Pregnant FVB mice were treated with dexamethasone (0.1 mg/kg or 1 mg/kg; s.c.) or vehicle (saline) from either embryonic day (E)9.5-15.5 or E12.5-E18.5 and then injected with [3H]digoxin (i.v.) to assess placental P-gp function. Dexamethasone treatment from E12.5-E18.5 significantly up-regulated Abcb1a mRNA (1 mg/kg) and P-gp (0.1 mg/kg and 1 mg/kg) expression on E18.5; however, this did not correlate to changes in drug accumulation in the fetal compartment. Similarly,...Continue Reading

Citations

Mar 8, 2012·Reproduction, Fertility, and Development·O R VaughanA L Fowden
Nov 8, 2015·Human Reproduction Update·E BloiseS G Matthews
Jan 21, 2015·Expert Opinion on Drug Metabolism & Toxicology·Frantisek Staud, Martina Ceckova
Dec 2, 2014·Pharmacology & Therapeutics·Renata SilvaFernando Remião
Jan 10, 2012·International Journal of Pharmaceutics·Bin MaGe Lin
Jan 24, 2012·Placenta·M IqbalS G Matthews
May 13, 2015·The American Journal of Pathology·Phetcharawan LyeStephen G Matthews
Oct 11, 2015·Seminars in Perinatology·Maisa FeghaliSteve Caritis
Nov 4, 2016·Pharmaceutical Research·Anand A JoshiPhillip M Gerk
Feb 22, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Enrrico BloiseStephen G Matthews
May 24, 2011·Reproductive Sciences·Sophie PetropoulosStephen G Matthews
Apr 25, 2018·Journal of Cellular and Molecular Medicine·Phetcharawan LyeStephen G Matthews
Jul 17, 2018·Expert Opinion on Drug Metabolism & Toxicology·Lyrialle W HanQingcheng Mao
Apr 12, 2018·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Matthew W KempSarah J Stock
Feb 25, 2018·Pharmaceutical Research·Nino TetroSara Eyal
Sep 28, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Clifford W MasonCarl P Weiner
Apr 30, 2021·Development·Cécile DemarezMariana Astiz
Oct 8, 2021·The Journal of Antimicrobial Chemotherapy·Nadia M IkumiMushi Matjila

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