Abstract：
In vertebrates, the hypothalamus-pituitary-adrenal gland (HPA) axis is the main endocrine pathway regulating the stress response, thus also called the stress axis. It has been well-accepted that the stress axis is tightly controlled by both hypothalamic stimulators and inhibitors [e.g. corticotropin (ACTH)-releasing inhibitory factor (CRIF)]. However, the identity of authentic CRIF remains unclear for decades. Recently, neuropeptide W (NPW) was proved to be the physiological CRIF in chickens. Together with its functional receptor (NPBWR2), they play critical roles in attenuating the activity of the chicken stress axis. Because increasing pieces of evidence suggested that sex steroids could regulate the stress axis, using chicken as a model, we investigated whether the newly identified CRIF and its receptor are under the control of sex steroids in this study. Our results showed that: (1) expression of NPW-NPBWR2 in the hypothalamus-pituitary axis was sexually dimorphic and developmental stage-dependent; (2) progesterone (P4), rather than 17β-estradiol (E2) and dihydrotestosterone (DHT), could dose- and time-dependently upregulate NPBWR2 expression, which was accompanied with the decrease of ACTH synthesis and secretion, in cultured pituitary cells; (3) intraperitoneal injection of P4 could elevate the mRNA level of pituitary NPBWR2; (4) P4-stimulated NPBWR2 expression was relevant to both nPR-mediated genomic action and mPRs-triggered nongenomic route associated with MEK/ERK, PI3K/AKT cascade, and calcium influx. To our knowledge, our results discover a novel route of sex steroids in modulating the stress axis of chickens, which lays a foundation to reveal the complicated interaction network between reproduction and stress axes in chickens.
摘要：
在脊椎动物中，下丘脑-垂体-肾上腺(HPA)轴是调节应激反应的主要内分泌途径,因此也称为应力轴。众所周知，应力轴受到下丘脑刺激剂和抑制剂[例如促肾上腺皮质激素（ACTH）释放抑制因子（CRIF）]的严格控制。然而,几十年来，真正的CRIF的身份仍然不清楚。最近,神经肽W（NPW）被证明是鸡的生理性CRIF。连同其功能受体（NPBWR2），它们在减弱鸡应激轴的活性中起关键作用。因为越来越多的证据表明性类固醇可以调节压力轴，以鸡为模型，在这项研究中,我们调查了新发现的CRIF及其受体是否处于性类固醇的控制之下.我们的结果表明：（1）下丘脑-垂体轴中NPW-NPBWR2的表达呈性别二态和发育阶段依赖性；（2）孕酮（P4），而不是17β-雌二醇（E2）和二氢睾酮（DHT），可以剂量和时间依赖性地上调NPBWR2的表达，伴随着ACTH合成和分泌的减少，在培养的垂体细胞中；（3）腹腔注射P4可以提高垂体NPBWR2的mRNA水平；（4）P4刺激的NPBWR2表达与nPR介导的基因组作用和mPRs触发的与MEK/ERK相关的非基因组途径有关。PI3K/AKT级联,和钙的流入。据我们所知,我们的研究结果发现了一种调节鸡应激轴性类固醇的新途径，为揭示鸡繁殖与应激轴之间复杂的相互作用网络奠定了基础。
