Department of Neonatology and Pediatric Intensive Care, University Medicine Greifswald, 17475 Greifswald, Germany.
Department of Neurology, University Medicine Greifswald, 17475 Greifswald, Germany.
J Integr Neurosci. 2021 Mar 30;20(1):109-118. doi: 10.31083/j.jin.2021.01.333.
Preterm birth causes neurological deficits. Previously, we demonstrated that fetal zone steroids reduce hyperoxia-mediated cell death . In immature oligodendrocytes (OLN-93 cells), dehydroepiandrosterone + 17β-estradiol co-treatment had synergistic beneficial effects while signals were transduced through different receptors. In immature astrocytes (C6 cells), both hormones compete for the same receptor and no synergistic effects were observed. 17β-estradiol and progesterone drastically decrease while fetal zone steroids, mainly dehydroepiandrosterone, remain persistently high within preterm infants until term. Substitution of 17β-estradiol and progesterone does not improve neurological outcomes. We investigated the influence of dehydroepiandrosterone, 17β-estradiol or dehydroepiandrosterone + 17β-estradiol treatment in C6 or OLN-93 cells on steroid receptor availability and activation of intracellular signaling molecules in hyperoxic cell culture. We sought explanations of the observed synergistic effect in preliminary study. In C6 cells, the generated signaling of dehydroepiandrosterone + 17β-estradiol treatment has no synergistic effects. The combined effect on this particular pathway does not potentiate cell survival. In OLN-93 cells, we observed significant differences in the early generated signaling of 17β-estradiol + dehydroepiandrosterone treatment to either 17β-estradiol dehydroepiandrosterone alone but never to both at the same time. The latter finding needs, therefore, further investigation to explain synergistic effects. Nevertheless, we add insight into the receptor and signaling cascade alterations induced by 17β-estradiol, dehydroepiandrosterone or 17β-estradiol + dehydroepiandrosterone treatment of C6 and OLN-93 cells in hyperoxia.
早产会导致神经功能缺陷。此前，我们已经证实胎儿带甾体激素可减少高氧诱导的细胞死亡。在未成熟的少突胶质细胞（OLN-93 细胞）中，脱氢表雄酮+17β-雌二醇联合治疗具有协同有益作用，而信号则通过不同的受体转导。在未成熟的星形胶质细胞（C6 细胞）中，两种激素竞争相同的受体，未观察到协同作用。在早产儿中，胎儿带甾体激素（主要是脱氢表雄酮）持续升高，而 17β-雌二醇和孕酮水平则急剧下降，直到足月。替代 17β-雌二醇和孕酮并不能改善神经发育结局。我们研究了脱氢表雄酮、17β-雌二醇或脱氢表雄酮+17β-雌二醇处理在 C6 或 OLN-93 细胞中对高氧细胞培养中甾体激素受体可用性和细胞内信号分子激活的影响。我们试图从初步研究中寻找观察到的协同作用的解释。在 C6 细胞中，脱氢表雄酮+17β-雌二醇处理产生的信号没有协同作用。该特定途径的联合作用不能增强细胞存活。在 OLN-93 细胞中，我们观察到 17β-雌二醇+脱氢表雄酮处理的早期信号与单独使用 17β-雌二醇或脱氢表雄酮有显著差异，但从未同时使用两者。因此，需要进一步研究来解释协同作用。尽管如此，我们还是深入了解了 17β-雌二醇、脱氢表雄酮或 17β-雌二醇+脱氢表雄酮处理 C6 和 OLN-93 细胞在高氧环境下引起的受体和信号级联改变。
