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Med. Sci. 2015, 3(4), 124-137; doi:10.3390/medsci3040124

Effects of the ABCB1 (1199G > A) Polymorphism on Steroid Sex Hormone-Induced P-Glycoprotein Expression, ATPase Activity, and Hormone Efflux

Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China
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Author to whom correspondence should be addressed.
Academic Editor: Yu-Jia Chang
Received: 23 September 2015 / Revised: 10 November 2015 / Accepted: 16 November 2015 / Published: 1 December 2015
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Abstract

This study examined how the 1199G > A polymorphism in the ABCB1 gene encoding P-glycoprotein (P-gp) affects the protein’s expression, ATPase activity, and ability to pump female steroid sex hormones out of LLC-PK1 cells. The ABCB1 (1199G) or ABCB1 (1199A) allele was transfected into cells, which were incubated for 48 h with various hormone concentrations, then analyzed by Western blotting to examine expression of P-gp protein and by reverse transcription-polymerase chain reaction (RT-PCR) to examine expression of mRNA. Cells were also compared in terms of their transepithelial permeability to steroid sex hormones in the presence and absence of the specific P-gp inhibitor GF120918. P-gp ATPase activity induced by steroid sex hormones was also assayed. Estriol and ethynyl estradiol up-regulated levels of ABCB1 mRNA in a concentration-dependent manner, with ABCB1 (1199A) mRNA showing greater up-regulation than ABCB1 (1199G) mRNA. Estrone, estriol, and ethynyl estradiol were substrates of both types of P-gp in transepithelial permeability assays, and the ABCB1 (1199A) protein showed a significantly higher net efflux ratio for estrone (13.4 vs. 7.4, p < 0.005), estriol (5.6 vs. 3.3, p < 0.05), and ethynyl estradiol (12.7 vs. 5.3, p < 0.005). Induction of P-gp ATPase activity by ethynyl estradiol and progesterone increased with increasing hormone concentration, and the magnitude of stimulation was greater for ABCB1 (1199A) P-gp than for ABCB1 (1199G) P-gp. These results indicate that the ABCB1 (1199G > A) polymorphism influences steroid sex hormone-induced expression and function of P-gp, which may help to explain inter-patient differences in P-gp-mediated chemotherapy resistance in vivo. View Full-Text
Keywords: ABCB1 (1199G > A); polymorphism; P-gp; steroid sex hormone; transport ABCB1 (1199G >; A); polymorphism; P-gp; steroid sex hormone; transport
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Peng, R.; Zhang, H.; Zhang, Y.; Wei, D.-Y. Effects of the ABCB1 (1199G > A) Polymorphism on Steroid Sex Hormone-Induced P-Glycoprotein Expression, ATPase Activity, and Hormone Efflux. Med. Sci. 2015, 3, 124-137.

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