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Preterm birth causes neurological deficits. Previously, we demonstrated that fetal zone steroids reduce hyperoxia-mediated cell death in vitro. 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.

Preterm birth causes neurological deficits. Previously, we demonstrated that fetal zone steroids reduce hyperoxia-mediated cell death