Developmental origins of the human hypothalamic-pituitary-adrenal axis

ABSTRACT

Introduction: The developmental origins of disease or fetal programming model predicts that intrauterine exposures have life long consequences for physical and psychological health. Prenatal programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis is proposed as a primary mechanism by which early experiences are linked to later disease risk.

Areas covered: This review describes the development of the fetal HPA axis, which is determined by an intricately timed cascade of endocrine events during gestation and is regulated by an integrated maternal-placental-fetal steroidogenic unit. Mechanisms by which stress-induced elevations in hormones of maternal, fetal, or placental origin influence the structure and function of the emerging fetal HPA axis are discussed. Recent prospective studies documenting persisting associations between prenatal stress exposures and altered postnatal HPA axis function are summarized, with effects observed beginning in infancy into adulthood.

Expert commentary: The results of these studies are synthesized, and potential moderating factors are discussed. Promising areas of further research highlighted include epigenetic mechanisms and interactions between pre and postnatal influences.

KEYWORDS:

• Placenta
• cortisol
• CRH
• fetal programming
• prenatal stress
• HPA axis
• pregnancy
• development

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was funded by National Institutes of Health grants NS-41298, HD-51852, HD-28413, and HD-40967 and NIMH Conte Center award MH-96889.