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Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need

Nature volume 373, pages 427–432 (1995)Cite this article

Abstract

THE body responds to stress by activation of the hypothalamic–pituitary–adrenal (HPA) axis and release of glucocorticoids. Glucocorticoid production in the adult regulates carbohydrate and amino-acid metabolism, maintains blood pressure, and restrains the inflammatory response1. In the fetus, exogenous glucocorticoids accelerate maturation of lung2 and gastrointestinal enzyme systems3 and promote hepatic glycogen deposition4. Corticotropin releasing hormone (CRH), a 41-amino-acid neuropeptide produced in the paraventricular nucleus of the hypothalamus and many regions of the cerebral cortex5, 6, has been implicated in both the HPA axis7 and behavioural responses8 to stress. To define the importance of CRH in the response of the HPA axis to stress and fetal development, we have constructed a mammalian model of CRH deficiency by targeted mutation in embryonic stem (ES) cells9. We report here that corticotropin-releasing hormone-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, despite marked glucocorticoid deficiency, these mice exhibit normal growth, fertility and longevity, suggesting that the major role of glucocorticoid is during fetal rather than postnatal life.

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Authors and Affiliations

  1. Division of Endocrinology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Louis Muglia, Lauren Jacobson & Joseph A. Majzoub

  2. Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Pieter Dikkes

Authors
  1. Louis Muglia
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  2. Lauren Jacobson
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  3. Pieter Dikkes
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  4. Joseph A. Majzoub
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Muglia, L., Jacobson, L., Dikkes, P. et al. Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need. Nature 373, 427–432 (1995). https://doi.org/10.1038/373427a0

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