Wei Hao, Lee Annie, Zhang Qing, Felmlee Melanie A
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
Pharmaceutics. 2023 Sep 29;15(10):2404. doi: 10.3390/pharmaceutics15102404.
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.
质子和钠依赖性单羧酸转运体（MCTs/SMCTs）是通过肾脏对单羧酸底物的重吸收来决定肾脏清除率的因素。先前对完整雌性和雄性、去卵巢雌性和去势雄性的研究揭示了肾脏单羧酸转运体表达的激素调节作用，从而促使人们对个体激素的调节作用进行研究。本研究的目的是评估外源性性激素和跨性别激素对肾脏MCT1、MCT4、CD147和SMCT1 mRNA及膜结合蛋白表达的影响。去卵巢（OVX）雌性和去势（CST）雄性Sprague Dawley大鼠在采集肾脏前21天接受雌激素和/或孕激素、睾酮或相应的安慰剂治疗。使用qPCR和蛋白质印迹法对mRNA和膜蛋白水平进行定量测定。定量分析显示，雌激素/孕激素联合治疗降低了膜MCT1和MCT4的表达，增加了SMCT1的表达，而给予睾酮则增加了MCT1膜蛋白的表达。相关性分析表明，血浆17β-雌二醇与MCT1和MCT4膜表达呈负相关，而睾酮呈正相关。相反，SMCT1膜表达与17β-雌二醇和孕激素浓度呈正相关。在OVX和CST大鼠接受性激素和跨性别激素治疗后，MCT1、MCT4、CD147和SMCT1的肾脏表达因雌性和雄性激素而发生显著改变。需要进一步研究以了解性激素、性激素受体的复杂作用以及青春期对MCT/SMCT调节的影响。
