Kalyani Manu, Callahan Phyllis, Janik James M, Shi Haifei
Department of Biology, Miami University, Oxford, OH 45056, USA.
Int J Mol Sci. 2017 Jun 27;18(7):1370. doi: 10.3390/ijms18071370.
There is a complex collection of neuroendocrine function during the postpartum period. Prolactin (PRL) released by suckling stimulus and its PRL receptors (PRL-R) in the central nervous system (CNS) are involved in hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in lactating mammals including rodents and humans. It is not clear how long it takes to reestablish the attenuated HPA axis activity of lactating rats to a pre-pregnancy state after pup separation. We first tested the hypothesis that HPA axis activity in response to an acute stress in postpartum rats would return to a pre-pregnancy state after pup separation. Restraint stress for 30 min was performed at the end of pup separation as an acute stressor. Plasma levels of corticosterone (CORT) were measured following restraint stress or no-stress (control) in virgin rats and postpartum rats housed with their pups or with pup removal for different periods of time of one hour, 24 h, or eight days. We then tested the hypothesis that circulating PRL level and CNS PRL-R gene expression were involved in mediating the acute stress response in postpartum rats. Plasma levels of PRL and PRL-R mRNA levels in the choroid plexus of the CNS were determined in both no-stress and stress, virgin rats, and postpartum rats housed with their pups or with pup removal for various periods, and their correlation with plasma CORT levels was assessed. The results demonstrated that PRL levels declined to virgin state in all postpartum rats separated from their pups, including the dams with one-hour pup separation. Stress-induced HPA activity dampened in lactating rats housed with pups, and returned to the pre-pregnancy state after 24 h of pup separation when both circulating PRL level and CNS PRL-R expression were restored to a pre-pregnancy state. Additionally, basal plasma CORT and CNS PRL-R expression were significantly correlated in rats with various pup status. This study suggested that stress-induced HPA activation occurred when PRL-R expression was similar to the level of virgin females, indicating that PRL-R upregulation contributes to an attenuated HPA response to acute stress. Understanding neuroendocrine responses to stress during the postpartum period is critical to understand postpartum-related neuropsychiatric illnesses and to maintain mental health in postpartum women.
产后时期存在复杂的神经内分泌功能集合。哺乳刺激释放的催乳素（PRL）及其在中枢神经系统（CNS）中的PRL受体（PRL-R）参与了包括啮齿动物和人类在内的哺乳类动物下丘脑-垂体-肾上腺（HPA）轴的低反应性。尚不清楚哺乳期大鼠在幼崽分离后，其减弱的HPA轴活动需要多长时间才能恢复到孕前状态。我们首先测试了一个假设，即产后大鼠对急性应激的HPA轴活动在幼崽分离后会恢复到孕前状态。在幼崽分离结束时进行30分钟的束缚应激作为急性应激源。在未应激（对照）的成年大鼠以及与幼崽一起饲养或幼崽被移除不同时间段（1小时、24小时或8天）的产后大鼠中，测量束缚应激或无应激后的血浆皮质酮（CORT）水平。然后我们测试了另一个假设，即循环PRL水平和CNS中PRL-R基因表达参与介导产后大鼠的急性应激反应。在未应激和应激状态下，分别测定成年大鼠以及与幼崽一起饲养或幼崽被移除不同时间段的产后大鼠的血浆PRL水平和CNS脉络丛中的PRL-R mRNA水平，并评估它们与血浆CORT水平的相关性。结果表明，所有与幼崽分离的产后大鼠，包括幼崽分离1小时的母鼠，PRL水平均降至成年状态。与幼崽一起饲养的哺乳期大鼠应激诱导的HPA活性减弱，在幼崽分离24小时后，当循环PRL水平和CNS PRL-R表达均恢复到孕前状态时，HPA活性恢复到孕前状态。此外，在不同幼崽状态的大鼠中，基础血浆CORT和CNS PRL-R表达显著相关。这项研究表明，当PRL-R表达与成年雌性水平相似时，应激诱导的HPA激活发生，这表明PRL-R上调导致HPA对急性应激的反应减弱。了解产后时期对压力的神经内分泌反应对于理解产后相关神经精神疾病以及维持产后妇女的心理健康至关重要。
