Glucocorticoids as regulatory signals during intrauterine development
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Fowden, A., & Forhead, A. (2015). Glucocorticoids as regulatory signals during intrauterine development. Experimental Physiology, 100 1477-1487. https://doi.org/10.1113/EP085212
Glucocorticoids are important regulatory signals during intrauterine development. They act as maturational, environmental and programming signals that modify the developing phenotype to optimise offspring viability and fitness. They affect development of a wide range of fetal tissues by inducing changes in cellular expression of structural, transport and signalling proteins, which have widespread functional consequences at the whole organ and systems levels. Glucocorticoids, therefore, activate many of the physiological systems that have little function in utero but are vital at birth to replace the respiratory, nutritive and excretory functions previously carried out by the placenta. However, by switching tissues from accretion to differentiation, early glucocorticoid overexposure in response to adverse conditions can program fetal development with longer term physiological consequences for the adult offspring which can extend to the next generation. The developmental effects of the glucocorticoids can be direct on fetal tissues with glucocorticoid receptors or mediated by changes in placental function or other endocrine systems. At the molecular level, glucocorticoids can act directly on gene transcription via their receptors or indirectly by epigenetic modifications of the genome. This review examines the role and functional significance of glucocorticoids as regulatory signals during intrauterine development and discusses the mechanisms by which they act in utero to alter the developing epigenome and ensuing phenotype.
Glucocorticoids, fetus, placenta, development, programming
We would like to thank the many members of the Department of Physiology, Development and Neuroscience who have contributed to discussions and helped with our own studies cited here. We are also grateful for financial support from the BBSRC (BB/I011773/1), Horserace Betting Levy Board (VET/PRJ/736) and the Centre for Trophoblast Research at the University of Cambridge.
External DOI: https://doi.org/10.1113/EP085212
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248546