Terenina Elena, Iannuccelli Nathalie, Billon Yvon, Fève Katia, Gress Laure, Bazovkina Darya, Mormede Pierre, Larzul Catherine
GenPhySE, INRAE, ENVT, Université de Toulouse, Castanet Tolosan, France.
GenESI, INRAE, Surgères, France.
Front Genet. 2025 Mar 12;16:1461385. doi: 10.3389/fgene.2025.1461385. eCollection 2025.
In facing the challenge of sustainability, animal breeding provides the option to improve animal robustness. In the search for new selection criteria related to robustness, the hypothalamic-pituitary-adrenocortical (HPA) axis is studied as a major neuroendocrine system involved in metabolic regulations and adaptive responses. Indeed, HPA axis activity is strongly influenced by genetic factors acting at several levels of the axis. The adrenocorticotropic hormone (ACTH) stimulation test has long been used to analyze interindividual and genetic differences in HPA axis activity in several species, including pigs. To uncover the genetic determinism of HPA activity and its influence on functional traits and robustness, a divergent selection experiment was carried out for three generations in a Large White pig population based on plasma cortisol levels measured one hour after injection of ACTH. In the present study the response to selection was very strong (confirming our previous studies), with a heritability value of cortisol level after ACTH injections reaching 0.64 (±0.03). The difference between the two divergent lines was around five genetic standard deviations after three selection steps. A genome-wide association study pointed out the importance of the glucocorticoid receptor gene () in this response. The measurement of plasma corticosteroid-binding globulin (CBG) binding capacity excluded any significant role of CBG in this selection process. The phenotypic effect of selection on body weight and growth rate was modest and/or inconsistent across generations. The HPA axis, a major neuroendocrine system involved in adaptation processes is highly heritable and responsive to genetic selection. The present experiment confirms the importance of glucocorticoid receptor polymorphism in genetic variation of HPA axis activity-in addition to the previously demonstrated role of CBG gene polymorphism. Further studies will explore the effect of this divergent selection on production and robustness.
面对可持续发展的挑战，动物育种提供了提高动物健壮性的选择。在寻找与健壮性相关的新选择标准时，下丘脑 - 垂体 - 肾上腺皮质（HPA）轴作为参与代谢调节和适应性反应的主要神经内分泌系统受到研究。事实上，HPA轴的活动受到在该轴多个水平起作用的遗传因素的强烈影响。促肾上腺皮质激素（ACTH）刺激试验长期以来一直用于分析包括猪在内的多个物种中HPA轴活动的个体间差异和遗传差异。为了揭示HPA活性的遗传决定因素及其对功能性状和健壮性的影响，基于注射ACTH一小时后测量的血浆皮质醇水平，在大白猪群体中进行了三代的分化选择实验。在本研究中，选择反应非常强烈（证实了我们之前的研究），ACTH注射后皮质醇水平的遗传力值达到0.64（±0.03）。经过三个选择步骤后，两个分化品系之间的差异约为五个遗传标准差。全基因组关联研究指出糖皮质激素受体基因（）在这种反应中的重要性。血浆皮质类固醇结合球蛋白（CBG）结合能力的测量排除了CBG在该选择过程中的任何显著作用。选择对体重和生长速率的表型效应在各代中适度且/或不一致。HPA轴作为参与适应过程的主要神经内分泌系统具有高度遗传性，并且对遗传选择有反应。本实验证实了糖皮质激素受体多态性在HPA轴活性遗传变异中的重要性——除了先前证明的CBG基因多态性的作用。进一步的研究将探索这种分化选择对生产和健壮性的影响。
