Sex differences in physiology are noted in clinical and animal studies. However, mechanisms underlying these observed differences between males and females remain elusive. Nuclear receptors control a wide range of physiological pathways and are expressed in the gastrointestinal tract, including the mouth, stomach, liver and intestine. We investigated the literature pertaining to ER, AR, FXR, and PPAR regulation and highlight the sex differences in nutrient metabolism along the digestive system. We chose these nuclear receptors based on their metabolic functions, and hormonal actions. Intriguingly, we noted an overlap in target genes of ER and FXR that modulate mucosal integrity and GLP-1 secretion, whereas overlap in target genes of PPARα with ER and AR modulate lipid metabolism. Sex differences were seen not only in the basal expression of nuclear receptors, but also in activation as their endogenous ligand concentrations fluctuate depending on nutrient availability. Finally, in this review, we speculate that interactions between the nuclear receptors may influence overall metabolic decisions in the gastrointestinal tract in a sex-specific manner.

在临床和动物研究中注意到生理学的性别差异。然而，这些观察到的男性和女性之间差异背后的机制仍然难以捉摸。核受体控制着广泛的生理途径，并在胃肠道中表达，包括口腔、胃、肝脏和肠道。我们调查了有关 ER、AR、FXR 和 PPAR 调节的文献，并强调了消化系统营养代谢的性别差异。我们根据它们的代谢功能和激素作用选择了这些核受体。有趣的是，我们注意到调节粘膜完整性和 GLP-1 分泌的 ER 和 FXR 的靶基因重叠，而 PPARα 的靶基因与 ER 和 AR 的重叠调节脂质代谢。性别差异不仅体现在核受体的基础表达中，而且还体现在激活中，因为它们的内源性配体浓度会根据营养物质的可用性而波动。最后，在这篇综述中，我们推测核受体之间的相互作用可能会以性别特异性方式影响胃肠道的整体代谢决定。