Dadam Florencia M, Cisternas Carla D, Macchione Ana F, Godino Andrea, Antunes-Rodrigues José, Cambiasso María J, Vivas Laura M, Caeiro Ximena E
Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.
Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, FMRP, USP, Brazil.
Mol Cell Endocrinol. 2017 May 15;447:98-105. doi: 10.1016/j.mce.2017.02.041. Epub 2017 Feb 27.
This study aimed to define whether sex chromosome complement (SCC) may differentially modulate sex differences in relative gene expression of basal Agtr1a, Agtr2, and Mas1 receptors at fore/hindbrain nuclei and at medulla/cortical kidney. Samples were collected from gonadectomized male (XX and XY) and female (XX and XY) mice of the "four core genotypes" model. At brain level, a SCC effect at the area postrema was demonstrated. An increase in mRNA level of Agtr1a and Agtr1a/Agtr2 ratio in XY-SCC mice was associated with a decrease in Mas1 compared to XX-SCC mice. In the renal cortex, a SCC effect for Agtr2 and Mas1 was observed. Regardless of sex (male or female), XX-SCC mice expressed higher levels of mRNA Agtr2 and Mas1 than XY-SCC mice {F(1,12) = 6,126,p < 0.05; F(1,21) = 5,143,p < 0.05}. Furthermore, XX-female mice showed a significant increase in Mas1 expression compared to XY-female mice. These results reveal a SCC modulatory effect at central and kidney level on angiotensin receptor expression, with an enhancement of the vasodilatory arm in XX-mice and an increase in the vasoconstriction arm in XY-mice, which may underlie sex differences in the regulation of arterial pressure.
本研究旨在确定性染色体组成(SCC)是否可能对前脑/后脑核以及延髓/肾皮质中基础Agtr1a、Agtr2和Mas1受体的相对基因表达中的性别差异进行差异性调节。从“四核心基因型”模型的去势雄性(XX和XY)和雌性(XX和XY)小鼠中采集样本。在脑水平上,已证实在最后区存在SCC效应。与XX-SCC小鼠相比,XY-SCC小鼠中Agtr1a的mRNA水平升高以及Agtr1a/Agtr2比值升高与Mas1降低相关。在肾皮质中,观察到Agtr2和Mas1存在SCC效应。无论性别(雄性或雌性),XX-SCC小鼠比XY-SCC小鼠表达更高水平的mRNA Agtr2和Mas1 {F(1,12) = 6.126,p < 0.05;F(1,21) = 5.143,p < 0.05}。此外,与XY雌性小鼠相比,XX雌性小鼠的Mas1表达显著增加。这些结果揭示了SCC在中枢和肾脏水平对血管紧张素受体表达的调节作用,XX小鼠中血管舒张臂增强,XY小鼠中血管收缩臂增加,这可能是动脉血压调节中性别差异的基础。