CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
Mol Neurobiol. 2021 Apr;58(4):1846-1858. doi: 10.1007/s12035-020-02267-9. Epub 2021 Jan 6.
Among the more than 300 functions attributed to prolactin (PRL), this hormone has been associated with the induction of neurogenesis and differentiation of olfactory neurons especially during pregnancy, which are essential for maternal behavior. Despite the original hypothesis that PRL enters the central nervous system through a process mediated by PRL receptors (PRLR) at the choroid plexus (CP), recent data suggested that PRL transport into the brain is independent of its receptors. Based on transcriptomic data suggesting that PRL could be expressed in the CP, this work aimed to confirm PRL synthesis and secretion by CP epithelial cells (CPEC). The secretion of PRL and the distribution of PRLR in CPEC were further characterized using an in vitro model of the rat blood-cerebrospinal fluid barrier. RT-PCR analysis of PRL transcripts showed its presence in pregnant rat CP, in CPEC, and in the rat immortalized CP cell line, Z310. These observations were reinforced by immunocytochemistry staining of PRL in CPEC and Z310 cell cytoplasm. A 63-kDa immunoreactive PRL protein was detected by Western blot in CP protein extracts as well as in culture medium incubated with rat pituitary and samples of rat cerebrospinal fluid and serum. Positive immunocytochemistry staining of PRLR was present throughout the CPEC cytoplasm and in the apical and basal membrane of these cells. Altogether, our evidences suggest that CP is an alternative source of PRL to the brain, which might impact neurogenesis of olfactory neurons at the subventricular zone, given its proximity to the CP.
在催乳素(PRL)的 300 多种功能中,这种激素与诱导神经发生和嗅觉神经元的分化有关,特别是在怀孕期间,这对母性行为至关重要。尽管最初的假设是 PRL 通过脉络丛(CP)中的 PRL 受体(PRLR)介导的过程进入中枢神经系统,但最近的数据表明 PRL 进入大脑的过程与其受体无关。基于转录组数据表明 PRL 可能在 CP 中表达,本工作旨在证实 CP 上皮细胞(CPEC)合成和分泌 PRL。使用大鼠血脑屏障的体外模型进一步表征了 PRL 的分泌和 PRLR 在 CPEC 中的分布。PRL 转录本的 RT-PCR 分析显示其存在于怀孕大鼠 CP、CPEC 和大鼠永生化 CP 细胞系 Z310 中。免疫细胞化学染色显示 PRL 在 CPEC 和 Z310 细胞质中的存在进一步证实了这一点。Western blot 在 CP 蛋白提取物以及用大鼠垂体孵育的培养基和大鼠脑脊液和血清样本中检测到 63 kDa 的免疫反应性 PRL 蛋白。PRLR 的免疫细胞化学染色阳性存在于 CPEC 的整个细胞质以及这些细胞的顶膜和基底膜中。总之,我们的证据表明 CP 是大脑中 PRL 的替代来源,由于其靠近 CP,它可能会影响侧脑室区嗅觉神经元的神经发生。