Brunton P J, Russell J A, Douglas A J
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, Edinburgh, UK.
J Neuroendocrinol. 2008 Jun;20(6):764-76. doi: 10.1111/j.1365-2826.2008.01735.x.
Over the past 40 years, it has been recognised that the maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations through pregnancy and lactation that might contribute to avoidance of adverse effects of stress on the mother and offspring. The extent of the global adaptations in the HPA axis has been revealed and the underlying mechanisms investigated within the last 20 years. Both basal, including the circadian rhythm, and stress-induced adrenocorticotrophic hormone and glucocorticoid secretory patterns are altered. Throughout most of pregnancy, and in lactation, these changes predominantly reflect reduced drive by the corticotropin-releasing factor (CRF) neurones in the parvocellular paraventricular nucleus (pPVN). An accompanying profound attenuation of HPA axis responses to a wide variety of psychological and physical stressors emerges after mid-pregnancy and persists until the end of lactation. Central to this suppression of stress responsiveness is reduced activation of the pPVN CRF neurones. This is consequent on the reduced effectiveness of the stimulation of brainstem afferents to these CRF neurones (for physical stressors) and of altered processing by limbic structures (for emotional stressors). The mechanism of reduced CRF neurone responses to physical stressors in pregnancy is the suppression of noradrenaline release in the PVN by an up-regulated endogenous opioid mechanism, which is induced by neuroactive steroid produced from progesterone. By contrast, in lactation suckling the young provides a neural stimulus that dampens the HPA axis circadian rhythm and reduces stress responses. Reduced noradrenergic input activity is involved in reduced stress responses in lactation, although central prolactin action also appears important. Such adaptations limit the adverse effects of excess glucocorticoid exposure on the foetus(es) and facilitate appropriate metabolic and immune responses.
在过去40年里，人们已经认识到，母体下丘脑-垂体-肾上腺（HPA）轴在妊娠和哺乳期间会发生适应性变化，这可能有助于避免压力对母亲和后代产生不利影响。在过去20年里，HPA轴整体适应性变化的程度已被揭示，其潜在机制也得到了研究。基础状态下（包括昼夜节律）以及应激诱导的促肾上腺皮质激素和糖皮质激素分泌模式均发生改变。在妊娠的大部分时间以及哺乳期，这些变化主要反映了小细胞室旁核（pPVN）中促肾上腺皮质激素释放因子（CRF）神经元的驱动作用减弱。妊娠中期后，HPA轴对多种心理和身体应激源的反应会出现显著减弱，并持续到哺乳期结束。这种应激反应性抑制的核心是pPVN中CRF神经元的激活减少。这是由于脑干传入神经对这些CRF神经元的刺激作用（针对身体应激源）有效性降低，以及边缘结构的处理过程改变（针对情绪应激源）所致。妊娠期间CRF神经元对身体应激源反应减弱的机制是，孕酮产生的神经活性类固醇诱导内源性阿片类机制上调，从而抑制PVN中去甲肾上腺素的释放。相比之下，在哺乳期，哺乳幼崽会提供一种神经刺激，减弱HPA轴的昼夜节律并降低应激反应。哺乳期应激反应降低涉及去甲肾上腺素能输入活动减少，尽管中枢催乳素的作用似乎也很重要。这些适应性变化限制了过量糖皮质激素暴露对胎儿的不利影响，并促进了适当的代谢和免疫反应。
