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 + 17-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.
17-estradiol and progesterone drastically decrease while fetal zone
steroids, mainly dehydroepiandrosterone, remain persistently high within preterm
infants until term. Substitution of 17-estradiol and progesterone does
not improve neurological outcomes. We investigated the influence of
dehydroepiandrosterone, 17-estradiol or dehydroepiandrosterone +
17-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 + 17-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 17-estradiol +
dehydroepiandrosterone treatment to either 17-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 17-estradiol, dehydroepiandrosterone or 17-estradiol
+ dehydroepiandrosterone treatment of C6 and OLN-93 cells in hyperoxia.