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Developmental origins of the human hypothalamic-pituitary-adrenal axis

Mariann A Howland1, Curt A Sandman1, Laura M Glynn1,2

  • 1a Department of Psychiatry and Human Behavior , University of California , Irvine , CA , USA.

Expert Review of Endocrinology & Metabolism
|July 31, 2018
PubMed

Insights

Prenatal exposures can program the fetal hypothalamic-pituitary-adrenal (HPA) axis, influencing lifelong health. This review details HPA axis development and how maternal stress impacts fetal programming, linking early life stress to later disease risk.

Area of Science:

  • Developmental Origins of Disease
  • Endocrinology
  • Neuroscience

Background:

  • The developmental origins of disease model posits that intrauterine exposures have lifelong health consequences.
  • Prenatal programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis is a key mechanism linking early experiences to later disease risk.

Purpose of the Study:

  • To review the development of the fetal HPA axis during gestation.
  • To discuss mechanisms by which maternal and fetal stress hormones influence HPA axis development.
  • To summarize evidence linking prenatal stress to altered HPA axis function postnatally.

Main Methods:

  • Review of endocrine events during gestation regulating fetal HPA axis development.
  • Analysis of mechanisms of maternal-placental-fetal steroidogenic unit.
  • Synthesis of prospective studies on prenatal stress and HPA axis function.

Main Results:

  • Fetal HPA axis development is a complex, timed cascade regulated by a maternal-placental-fetal unit.
  • Maternal, fetal, or placental stress hormones can alter fetal HPA axis structure and function.
  • Prenatal stress exposures are associated with persistent alterations in HPA axis function from infancy to adulthood.

Conclusions:

  • Prenatal programming of the HPA axis is a critical pathway for developmental origins of disease.
  • Epigenetic mechanisms and pre- and postnatal interactions are promising areas for future research.
Abstract

Keywords:
CRHHPA axisPlacentacortisoldevelopmentfetal programmingpregnancyprenatal stress

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