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Sex differences in hepatic MCT1 and CD147 expression
Author(s) -
Cao Jieyun,
Ng Michael,
Felmlee Melanie A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1062.4
Subject(s) - estrous cycle , endocrinology , medicine , messenger rna , ovariectomized rat , ketone bodies , western blot , biology , testosterone (patch) , hormone , chemistry , metabolism , gene , biochemistry
Purpose Monocarboxylate transporter 1 (MCT) belongs to the solute carrier super family, and transports monocarboxylates such as ketone bodies, lactate and pyruvate, as well as drugs such as gamma‐hydroxybutyric acid. CD147 interacts with MCT1 as an ancillary protein for trafficking to the plasma membrane. Previously, it has been shown that MCT expression changes under different sex hormone conditions in skeletal muscle and Sertoli cells. However, it is unknown if MCT1 or CD147 demonstrates sex differences in the liver where MCT1 play an important role in drug disposition. The purpose of this study is to evaluate hepatic MCT1 and CD147 mRNA and protein expression in males, over the estrus cycle in female rats and in the absence of female sex hormones. Method Liver samples were harvested from 6 groups of rats (N = 3 – 5 per group): females at the four stages of the estrus cycle (proestrus, estrus, metestrus, diestrus), ovariectomized (OVX) females and male Sprague‐Dawley rats. Estrus cycle stages of females were classified by vaginal lavage smear. Hepatic mRNA expression of MCT1 and CD147 were analyzed by qPCR. Whole cell and membrane protein expression of MCT1 and CD147 were evaluated by western blot. Results MCT1 mRNA expression was significantly lower (0.4 and 0.3 fold respectively) in proestrus and metestrus compared to control (male rats). OVX and male rats showed similar MCT1 mRNA and whole cell protein expression. Membrane MCT1 expression in proestrus, metestrus, and diestrus groups was significantly lower (21% – 42%) compared to OVX rats. MCT1 total and membrane protein expression were positively correlated (r = 0.69). Hepatic membrane bound ancillary protein CD147 in males was significantly higher (2.3 – 3 times) than other groups whereas mRNA and whole protein expression did not show any difference. Conclusion MCT1 mRNA expression is lower in the presence of female sex hormones indicating they play a role in reducing MCT1 mRNA expression in liver. Ovariectomy increased membrane MCT1 expression compared to female rats indicating female hormones negatively regulate MCT1 membrane expression. Significant sex differences were observed in membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels demonstrating that androgens are involved in regulating CD147 membrane localization. This study reveals that hepatic MCT1 and CD147 expression and localization were regulated by sex hormones. Sex differences in hepatic MCT1 expression may lead to altered drug disposition of its substrates, so it is critical to understand the role of sex hormones and MCT1 regulation.