IMR Press / JIN / Volume 20 / Issue 1 / DOI: 10.31083/j.jin.2021.01.333
Open Access Short Communication
The neuroendocrine effects of dehydroepiandrosterone and 17β-estradiol in the in vitro preterm hyperoxia infant model
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1 Department of Neonatology and Pediatric Intensive Care, University Medicine Greifswald, 17475 Greifswald, Germany
2 Department of Neurology, University Medicine Greifswald, 17475 Greifswald, Germany
3 Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, 80636 Munich, Germany
*Correspondence: (Matthias Heckmann)
These authors contributed equally.
J. Integr. Neurosci. 2021, 20(1), 109–118;
Submitted: 15 October 2020 | Revised: 4 January 2021 | Accepted: 8 February 2021 | Published: 30 March 2021
Copyright: © 2021 The Authors. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

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.

Fetal zone steroid
Preterm infant
Estrogen receptor
Androgen receptor
Fig. 1.
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