Kadhim Hakeem J, Kuenzel Wayne J
Veterinary Medicine College, University of Thi-Qar, Nasiriyah, Iraq.
Poultry Science, University of Arkansas, Fayetteville, AR, United States.
Front Physiol. 2022 Oct 18;13:972171. doi: 10.3389/fphys.2022.972171. eCollection 2022.
The location of corticotropin-releasing hormone receptor 2 (CRH-R2) on thyrotropes within the avian anterior pituitary (APit) and its activation by different stressors indicate a possible communication between hypothalamo-pituitary-adrenal (HPA) and thyroid (HPT) axes. Therefore, an experiment was designed to 1) compare the timing of major components of the HPT axis to those of the HPA axis; 2) address whether stressors activating the HPA axis may simultaneously upregulate components of the HPT axis. Blood, brain, and APit were sampled from chicks prior to stress (control) and 15, 30, 60, 90, and 120 min following immobilization (IM) stress. The nucleus of the hippocampal commissure (NHpC) and paraventricular nucleus (PVN) were cryo-dissected from brains for RT-qPCR. Gene expression of thyrotropin-releasing hormone (TRH) and its receptors (TRH-R1 and TRH-R3), urocortin3 (UCN3), deiodinase 2 (D2), and the second type of corticotropin-releasing hormone (CRH2) within the NHpC and PVN was measured. Additionally, gene expression of TRH receptors, thyroid stimulating hormone subunit beta (TSHβ), and D2 was determined in the APit and corticosterone assayed in blood. In brains, a significant upregulation in examined genes occurred at different times of IM. Specifically, UCN3 and CRH2 which have a high affinity to CRH-R2 showed a rapid increase in their mRNA levels that were accompanied by an early upregulation of TRHR1 in the NHpC. In the APit, a significant increase in gene expression of TSHβ and TRH receptors was observed. Therefore, results supported concurrent activation of major brain and APit genes associated with the HPA and HPT axes following IM. The initial neural gene expression originating within the NHpC resulted in the increase of TSHβ mRNA in the APit. Specifically, the rapid upregulation of UCN3 in the NHpC appeared responsible for the early activation of TSHβ in the APit. While sustaining TSHβ activation appeared to be due to both CRH2 and TRH. Therefore, data indicate that CRH-producing neurons and corticotropes as well as CRH- and TRH-producing neurons and thyrotropes are activated to produce the necessary energy required to maintain homeostasis in birds undergoing stress. Overall, data support the inclusion of the NHpC in the classical avian HPA axis and for the first time show the concurrent activation of the HPA axis and components of the HPT axis following a psychogenic stressor.
促肾上腺皮质激素释放激素受体2（CRH-R2）在禽类腺垂体（APit）内促甲状腺激素细胞上的定位及其被不同应激源激活，表明下丘脑-垂体-肾上腺（HPA）轴与甲状腺（HPT）轴之间可能存在通讯联系。因此，设计了一项实验来：1）比较HPT轴主要成分与HPA轴主要成分的时间变化；2）探讨激活HPA轴的应激源是否会同时上调HPT轴的成分。在应激前（对照）以及固定（IM）应激后15、30、60、90和120分钟，从雏鸡采集血液、脑和APit样本。从脑中冷冻解剖出海马连合核（NHpC）和室旁核（PVN）用于RT-qPCR。测量NHpC和PVN内促甲状腺激素释放激素（TRH）及其受体（TRH-R1和TRH-R3）、尿皮质素3（UCN3）、脱碘酶2（D2）以及第二种促肾上腺皮质激素释放激素（CRH2）的基因表达。此外，测定APit中TRH受体、促甲状腺激素β亚基（TSHβ）和D2的基因表达，并检测血液中的皮质酮水平。在脑中，IM应激不同时间后，所检测基因出现显著上调。具体而言，对CRH-R2具有高亲和力的UCN3和CRH2，其mRNA水平迅速升高，同时NHpC中的TRHR1早期上调。在APit中，观察到TSHβ和TRH受体的基因表达显著增加。因此，结果支持IM应激后与HPA轴和HPT轴相关的主要脑区和APit基因同时被激活。源自NHpC的初始神经基因表达导致APit中TSHβ mRNA增加。具体来说，NHpC中UCN3的快速上调似乎是APit中TSHβ早期激活的原因。而维持TSHβ激活似乎是由于CRH2和TRH两者。因此，数据表明，产生CRH的神经元和促肾上腺皮质激素细胞以及产生CRH和TRH的神经元和促甲状腺激素细胞被激活，以产生维持应激状态下鸟类体内稳态所需的能量。总体而言，数据支持将NHpC纳入经典的禽类HPA轴，并且首次显示了心理应激源后HPA轴和HPT轴成分的同时激活。
