REVIEW article
Front. Endocrinol.
Sec. Developmental Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1587891
Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications
Provisionally accepted
- Loma Linda University, Loma Linda, United States
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Glucocorticoids are steroid hormones that regulate multiple physiological processes across the lifespan and play a central role in the adaptive stress response. Their biological effects are mediated by the glucocorticoid receptor that acts via genomic and non-genomic mechanisms to regulate transcriptional signatures and intracellular signaling, respectively. These effects are tissue-and context-dependent as the body adapts to developmental and environmental changes. Glucocorticoid-mediated effects are determined by both their bioavailability and the tissue response. Reduced glucocorticoid sensitivity has been observed in patients with severe disease or decreased response to synthetic glucocorticoid therapies. During the perinatal period, the endogenous glucocorticoid, cortisol, exerts unique developmental effects on the late-gestation fetus that are necessary for extrauterine life. Antenatal glucocorticoid therapy has shown beneficial effects in the prevention of prematurity-related diseases, while postnatal glucocorticoid reduces inflammation and improves oxygenation in bronchopulmonary dysplasia. However, these therapies are not devoid of variable responses in both beneficial and adverse effects. Furthermore, preterm newborns are exposed to adverse intrauterine environments, including placental insufficiency and infection, which, combined with immaturity, result in dysregulated perinatal glucocorticoid homeostasis. Therefore, intrauterine stressors can alter fetal glucocorticoid sensitivity, partially explaining the variability in clinical outcomes observed in preterm newborns. Adverse intrauterine environments can interact with genetic and physiological factors, such as gestational age and fetal sex, further amplifying the dysregulation of perinatal glucocorticoid homeostasis. In this review, we explore the clinical and basic science evidence on the endogenous determinants of perinatal glucocorticoid sensitivity, with emphasis on the clinical implications for disease risk and glucocorticoid therapy efficacy in the preterm newborn.
Keywords: corticosteroids, Glucocorticoid sensitivity, Glucocorticoid receptor, Intrauterine stress, Preterm neonate, Neonatal morbidity
Received: 05 Mar 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 Anti, Gheorghe, Deming, Adeoye, Zhang and Mata-Greenwood. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Eugenia Mata-Greenwood, Loma Linda University, Loma Linda, United States
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