Fetal programming of hypothalamo‐pituitary‐adrenal function: prenatal stress and glucocorticoids

Abstract

Prenatal stress (PS) and maternal exposure to exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal (HPA) function and stress-related behaviour. Both of these manipulations lead to increased fetal exposure to glucocorticoids. Glucocorticoids are essential for many aspects of normal brain development, but exposure of the fetal brain to an excess of glucocorticoids can have life-long effects on neuroendocrine function. Both endogenous glucocorticoid and synthetic glucocorticoid exposure have a number of rapid effects in the fetal brain, including modification of neurotransmitter systems and transcriptional machinery. Such fetal exposure permanently alters HPA function in prepubertal, postpubertal and ageing offspring, in a sex-dependent manner. Prenatal stress and exogenous glucocorticoid manipulation also lead to the modification of behaviour, brain and organ morphology, as well as altered regulation of other endocrine systems. It is also becoming increasingly apparent that the timing of exposure to PS or synthetic glucocorticoids has tremendous effects on the nature of the phenotypic outcome. Permanent changes in endocrine function will ultimately impact on health in both human and animal populations.

Prenatal Stress Enhances Responsiveness to Cocaine

“…The factors that induce the behavioral and neurochemical alterations observed following PNS were not examined in the present study but appear to stem from both stress hormones produced during the PNS procedure and subsequent alterations in mother-pup interactions. There is extensive evidence that PNS procedures induce neuroendocrine responses in both dam and pup and that elevations in hormones can program the developing fetus, biasing it towards many diseases, including psychopathology (for recent reviews see Kapoor et al, 2006;Knackstedt et al, 2005;Koenig et al, 2005;Seckl and Meaney, 2006;Weinstock, 2005). On the other hand, growing evidence suggests that PNS-induced alterations are mediated, at least in part, by alterations in maternal interactions with offspring following birth (Smith et al, 2004;Neumann et al, 2005;Champagne and Meaney, 2006).…”

An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population

“…Although we were not able to account for maternal effects prior to laying in our current study, there are many ways in which mothers influence their offspring's HPA axis activity. In mammals, prenatal CORT exposure and postnatal maternal care (such as grooming and time spent with offspring) can induce long-lasting changes in offspring HPA responsiveness mediated through epigenetic processes [31,55,56]. In avian species, variation in the amount of CORT deposited in egg yolks may have similar effects on offspring phenotype [57][58][59].…”

“…repeated handling or disturbance, populations with high predator prevalence) [21,31,54]. There is a critical window, typically throughout early development, during which the HPA axis is especially susceptible to permanent organizational changes in stress reactivity that could cause alterations in glucocorticoid secretion profiles and behavioural coping styles in subsequent years [10,55,56]. Because heritability estimates can be sensitive to capricious environmental parameters [41], captive studies provide a meaningful estimate of standing additive genetic variation underlying phenotypic variation within a narrow range of environmental contexts.…”

The persistent effects of in utero nutrition shocks over the life cycle: Evidence from Ramadan fasting

“…Recently, Dikensoy et al (2009) reported that Ramadan fasting is associated with increases in cortisol levels during pregnancy. This finding is of interest because cortisol is a stress hormone understood to potentially 'program' health in adulthood (Kapoor et al, 2006). Many studies give evidence that pregnant women in Ramadan do indeed reach low levels of blood glucose and high levels of ketones.…”

“…It is believed that in utero exposure to glucocorticoids such as cortisol leads to a reprogramming of the hypothalamic pituitary adrenal axis (HPA), which is linked with not only type 2 diabetes, high blood pressure but also cognitive impairment (Kapoor et al, 2006;Seckl and Holmes, 2007). Metzger et al (1982) were one of the very first to document the high level of ketones, free fatty acids and low glucose levels in pregnant women compared to non-pregnant women after 12 hours of nighttime fasting.…”