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。
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.