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Glucocorticoids and fetal programming part 1: outcomes

Nature Reviews Endocrinology volume 10, pages 391–402 (2014)Cite this article

Subjects

Key Points

  • Glucocorticoids are necessary for normal development and are particularly important for maturation of the fetal brain, lungs and kidneys

  • Exposure of the fetus to excess glucocorticoids leads to long-term programming of the function of the hypothalamic–pituitary–adrenal (HPA) axis and the behaviour of the organism

  • A number of similarities exist between outcomes identified in animal models and those emerging from human studies

  • Programming of the HPA axis by glucocorticoids is dynamic and changes as a function of age; the effects are sex-specific and dependent on the stage of development at exposure

  • The effects of synthetic glucocorticoid exposure or maternal stress can manifest in offspring for multiple generations

Abstract

Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic–pituitary–adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.

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Figure 1: Simplified schematic of the hypothalamic–pituitary–adrenal axis.

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Acknowledgements

The authors would like to acknowledge the support of grants from the Canadian Institutes of Health Research (126166) and the Natural Sciences and Engineering Research Council of Canada.

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Authors and Affiliations

  1. Department of Physiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, M5S 1A8, ON, Canada

    Vasilis G. Moisiadis

  2. Departments of Obstetrics and Gynaecology, Medicine and Physiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, M5S 1A8, ON, Canada

    Stephen G. Matthews

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Moisiadis, V., Matthews, S. Glucocorticoids and fetal programming part 1: outcomes. Nat Rev Endocrinol 10, 391–402 (2014). https://doi.org/10.1038/nrendo.2014.73

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