Effect of Sex and Cross-Sex Hormone Treatment on Renal Monocarboxylate-Transporter Expression in Rats

Abstract

Proton- and sodium-dependent monocarboxylate transporters (MCTs/SMCTs) are determinants of renal clearance through the renal reabsorption of monocarboxylate substrates. Prior studies with intact females and males, ovariectomized females and castrated males have revealed the hormonal regulation of renal monocarboxylate-transporter expression, prompting investigation into the regulatory role of individual hormones. The aim of the present study is to evaluate the effect of exogenous sex and cross-sex hormones on renal MCT1, MCT4, CD147 and SMCT1 mRNA and membrane-bound protein expression. Ovariectomized (OVX) females and castrated (CST) male Sprague Dawley rats received estrogen and/or progesterone, testosterone, or a corresponding placebo treatment for 21 days prior to kidney collection. The quantitative measurement of mRNA and membrane-protein levels were conducted using qPCR and Western blot. Quantitative analysis revealed the combination estrogen/progesterone treatment reduced membrane MCT1 and 4 expression and increased SMCT1 expression, while testosterone administration increased MCT1 membrane-protein expression. Correlation analysis indicated that plasma 17β-estradiol was negatively correlated with MCT1 and MCT4 membrane expression, while testosterone was positively correlated. In contrast, SMCT1 membrane expression was positively correlated with 17β-estradiol and progesterone concentrations. MCT1, MCT4, CD147 and SMCT1 renal expression are significantly altered in response to female and male sex hormones following sex and cross-sex hormone treatment in OVX and CST rats. Further studies are needed to understand the complex role of sex hormones, sex hormone receptors and the impact of puberty on MCT/SMCT regulation.