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Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs.
Biochem Biophys Res Commun 2019; 519(3):613-619BB

Abstract

P-glycoprotein (P-gp/ABCB1) is an ATP-binding cassette drug efflux transporter expressed in a variety of tissues that affects the pharmacokinetic disposition of many drugs. Although several studies have reported gender-dependent differences in the expression of P-gp, the role of sex hormones in regulating the expression of P-gp and its transport activity has not been well understood. In this study, we demonstrated that 17β-estradiol has the ability to induce the expression of P-pg in mouse kidneys and cultured human renal proximal tubular epithelial cells. After intravenous injection of a typical P-gp substrate, digoxin, renal clearance in female mice was approximately 2-fold higher than that in male mice. The expression of murine P-gp and its mRNA (Abcb1a and Abcb1b) were also higher in female mice than in male mice. The expression of P-gp in cultured renal tissues prepared from female and male mice was significantly increased by 17β-estradiol, but not testosterone. Similar 17β-estradiol-induced expression of P-gp was also detected in cultured human tubular epithelial cells, accompanied by the enhancement of its transport activity of digoxin. The present findings suggest the contribution of estradiol to female-predominant expression of P-gp in renal cells, which is associated with sex-related disparities in the renal elimination of digoxin.

Authors+Show Affiliations

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmacology, Faculty of Medicine, Oita University, 1-1, Idaigaoka Hasamamachi Yufu, Oita, 879-5593, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan; Department of Glocal Healthcare Science, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan; Department of Glocal Healthcare Science, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan. Electronic address: ohdo@phar.kyushu-u.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31540689

Citation

Kanado, Yuki, et al. "Estradiol Regulation of P-glycoprotein Expression in Mouse Kidney and Human Tubular Epithelial Cells, Implication for Renal Clearance of Drugs." Biochemical and Biophysical Research Communications, vol. 519, no. 3, 2019, pp. 613-619.
Kanado Y, Tsurudome Y, Omata Y, et al. Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs. Biochem Biophys Res Commun. 2019;519(3):613-619.
Kanado, Y., Tsurudome, Y., Omata, Y., Yasukochi, S., Kusunose, N., Akamine, T., ... Ohdo, S. (2019). Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs. Biochemical and Biophysical Research Communications, 519(3), pp. 613-619. doi:10.1016/j.bbrc.2019.09.021.
Kanado Y, et al. Estradiol Regulation of P-glycoprotein Expression in Mouse Kidney and Human Tubular Epithelial Cells, Implication for Renal Clearance of Drugs. Biochem Biophys Res Commun. 2019 Nov 12;519(3):613-619. PubMed PMID: 31540689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs. AU - Kanado,Yuki, AU - Tsurudome,Yuya, AU - Omata,Yuji, AU - Yasukochi,Sai, AU - Kusunose,Naoki, AU - Akamine,Takahiro, AU - Matsunaga,Naoya, AU - Koyanagi,Satoru, AU - Ohdo,Shigehiro, Y1 - 2019/09/17/ PY - 2019/08/21/received PY - 2019/09/07/accepted PY - 2019/9/22/pubmed PY - 2019/9/22/medline PY - 2019/9/22/entrez KW - 17β-estradiol KW - Clearance KW - Digoxin KW - P-glycoprotein KW - Renal KW - Testosterone SP - 613 EP - 619 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 519 IS - 3 N2 - P-glycoprotein (P-gp/ABCB1) is an ATP-binding cassette drug efflux transporter expressed in a variety of tissues that affects the pharmacokinetic disposition of many drugs. Although several studies have reported gender-dependent differences in the expression of P-gp, the role of sex hormones in regulating the expression of P-gp and its transport activity has not been well understood. In this study, we demonstrated that 17β-estradiol has the ability to induce the expression of P-pg in mouse kidneys and cultured human renal proximal tubular epithelial cells. After intravenous injection of a typical P-gp substrate, digoxin, renal clearance in female mice was approximately 2-fold higher than that in male mice. The expression of murine P-gp and its mRNA (Abcb1a and Abcb1b) were also higher in female mice than in male mice. The expression of P-gp in cultured renal tissues prepared from female and male mice was significantly increased by 17β-estradiol, but not testosterone. Similar 17β-estradiol-induced expression of P-gp was also detected in cultured human tubular epithelial cells, accompanied by the enhancement of its transport activity of digoxin. The present findings suggest the contribution of estradiol to female-predominant expression of P-gp in renal cells, which is associated with sex-related disparities in the renal elimination of digoxin. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/31540689/Estradiol_regulation_of_P-glycoprotein_expression_in_mouse_kidney_and_human_tubular_epithelial_cells,_implication_for_renal_clearance_of_drugs L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)31742-5 DB - PRIME DP - Unbound Medicine ER -