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The fetal and neonatal hypothalamic–pituitary–adrenal axis
  1. P C Ng
  1. Department of Paediatrics, Level 6, Clinical Science Building, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong, Peoples Republic of China
  1. Professor Ng

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The hypothalamus, pituitary, and adrenal glands are dynamic endocrine organs during fetal development.1-3 The adrenal glands, in particular, exhibit remarkable transformation in size, morphology, and function during the prenatal and neonatal periods.2 3 It is now recognised that normal development of the hypothalamic–pituitary–adrenal (HPA) axis is essential for: (1) the regulation of intrauterine homeostasis; and (2) the timely differentiation and maturation of vital organ systems including the lungs, liver, and central nervous system necessary for immediate neonatal survival after birth. In addition, acting together with the placenta, the HPA axis might indirectly control the normal timing of parturition in primates.1-3 The liberal use of exogenous antenatal and postnatal corticosteroids during pregnancy and early neonatal life have also raised concerns about potential adverse effects on the HPA axis and subsequent neurodevelopment.4 Thus, an understanding of the physiology and function of the HPA axis in intrauterine and extrauterine life is important for neonatologists. This article aims to provide an overview on the physiology of the glucocorticoid axis and the effects that exogenous corticosteroids have on this system.

Basic physiology

Hormone activity in the HPA axis can be detected between eight and 12 weeks of gestation, early in fetal development.1-3Corticotrophin releasing hormone (CRH) is produced from the fetal hypothalamus and the placenta during pregnancy. It is the primary secretagogue controlling pro-opiomelanocortin (POMC) mRNA expression and pituitary corticotroph secretion of adrenocorticotrophin (ACTH).1 3 CRH regulates the growth of pituitary corticotrophs, adrenocortical differentiation, and steroidogenic maturation of the fetal HPA axis.3 It is also a potent vasodilator of the fetoplacental circulation and can potentiate the function of local mediators and hormones, such as prostaglandins and oxytocin, in increasing myometrial contractility during labour.1 The progressive increase in the concentration of CRH in fetal and maternal circulations at late gestation …

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