Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

Authors

  • Jieyun Cao Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific.
  • Michael Ng Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific.
  • Melanie A Felmlee Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific.

DOI:

https://doi.org/10.18433/J3CH29

Abstract

Purpose: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females. Method: Liver samples were collected from females at the four estrous cycle stages (proestrus, estrus, metestrus, diestrus), OVX females and male Sprague-Dawley rats (N = 3 – 5). Estrus cycle stage of females was determined by vaginal lavage. mRNA and protein (total and membrane) expression of MCT1, MCT4 and CD147 was evaluated by qPCR and western blot analysis. Results: MCT1 mRNA and membrane protein expression varied with estrous cycle stage, with OVX females having higher expression than males, indicating that female sex hormones may play a role in MCT1 regulation. MCT4 membrane expression varied with estrous cycle stage with expression significantly lower than males. MCT4 membrane expression in OVX females was also lower than males, suggesting that androgens play a role in membrane expression of MCT4. Males had higher membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels suggesting that androgens are involved in regulating CD147 membrane localization. Conclusions: This study demonstrates hepatic expression and membrane localization of MCT1, MCT4 and CD147 are regulated by sex hormones. Sex differences in hepatic MCT expression may lead to altered drug disposition, so it is critical to elucidate the underlying mechanisms in the sex hormone-dependent regulation of MCT expression.

 

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Author Biography

Melanie A Felmlee, Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific.

Assistant Professor

Department of Pharmceutics & Medicinal Chemistry

Thomas J Long School of Pharmacy and Health Sciences

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Published

2018-01-09

How to Cite

Cao, J., Ng, M., & Felmlee, M. A. (2018). Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking. Journal of Pharmacy & Pharmaceutical Sciences, 20(1), 435–444. https://doi.org/10.18433/J3CH29

Issue

Section

Pharmaceutical Sciences; Original Research Articles