为了确保产妇行为在围产期的不受限制的表达,促肾上腺皮质激素释放因子(CRF)系统的活性需要最小化。CRF结合蛋白(CRF-BP)可能对这种适应至关重要,因为它的主要功能是隔离可自由获得的CRF和尿cortin1,从而抑制CRF受体(CRF-R)信号传导。到目前为止,CRF-BP在母体大脑中的作用几乎没有被研究过,和减少应力轴激活的潜在作用是未知的。我们研究了下丘脑室旁核(PVN)内CRF-BP和CRF-R的基因表达。在哺乳期的大鼠中,与原始大鼠相比,细小细胞PVN中的Crh-bp表达显着升高,而PVN中的Crh-r1表达显着降低。在无应力条件下,输注CRF(6-33)对PVN的急性CRF-BP抑制作用会增加大坝的基础血浆皮质酮浓度。此外,而急性PVN内输注CRF增加了原始大鼠的皮质酮分泌,在媒介物(VEH)预处理的哺乳期大鼠中无效,可能是由于CRF-BP的缓冲作用。的确,用CRF(6-33)预处理恢复了泌乳大鼠对CRF的皮质酮反应,强调CRF-BP在维持泌乳应激反应性减弱中的关键作用。据我们所知,这是首次将泌乳期下丘脑CRF-BP活性与下丘脑-垂体-肾上腺轴调节联系起来的研究.在行为方面,与VEH处理的大鼠相比,在非应激条件下PVN中的急性CRF-BP抑制减少了输注后60分钟的毯子护理和90分钟的舔/修饰,同时增加母亲对入侵者的侵略。最后,CRF-BP的慢性PVN内抑制可显著降低母体攻击性,对产妇的动机和护理有适度的影响。一起来看,产后期间PVN中CRF-BP的完整活动对于抑制压力轴的反应至关重要,以及充分表达适当的母性行为。
To ensure the unrestricted expression of maternal behaviour peripartum, activity of the corticotropin-releasing factor (CRF) system needs to be minimised. CRF binding protein (CRF-BP) might be crucial for this adaptation, as its primary function is to sequester freely available CRF and urocortin1, thereby dampening CRF receptor (CRF-R) signalling. So far, the role of CRF-BP in the maternal brain has barely been studied, and a potential role in curtailing activation of the stress axis is unknown. We studied gene expression for CRF-BP and both CRF-R within the paraventricular nucleus (
PVN) of the hypothalamus. In lactating rats, Crh-bp expression in the parvocellular PVN was significantly higher and Crh-r1 expression in the
PVN significantly lower compared to virgin rats. Acute CRF-BP inhibition in the PVN with infusion of CRF(6-33) increased basal plasma corticosterone concentrations under unstressed conditions in dams. Furthermore, while acute intra-
PVN infusion of CRF increased corticosterone secretion in virgin rats, it was ineffective in vehicle (VEH)-pre-treated lactating rats, probably due to a buffering effect of CRF-BP. Indeed, pre-treatment with CRF(6-33) reinstated a corticosterone response to CRF in lactating rats, highlighting the critical role of CRF-BP in maintaining attenuated stress reactivity in lactation. To our knowledge, this is the first study linking hypothalamic CRF-BP activity to hypothalamic-pituitary-adrenal axis regulation in lactation. In terms of behaviour, acute CRF-BP inhibition in the
PVN under non-stress conditions reduced blanket nursing 60 min and licking/grooming 90 min after infusion compared to VEH-treated rats, while increasing maternal aggression towards an intruder. Lastly, chronic intra-PVN inhibition of CRF-BP strongly reduced maternal aggression, with modest effects on maternal motivation and care. Taken together, intact activity of the CRF-BP in the
PVN during the postpartum period is essential for the dampened responsiveness of the stress axis, as well as for the full expression of appropriate maternal behaviour.