Glucocorticoid programming of pituitary-adrenal function: mechanisms and physiological consequences

Area of Science:

• Developmental biology
• Endocrinology
• Epidemiology

Background:

• Epidemiological studies link adverse fetal events to permanent physiological changes in offspring, termed 'fetal programming'.
• Low birth weight in humans correlates with increased risks of adult cardiovascular, metabolic, and neuroendocrine disorders.
• Glucocorticoids administered during pregnancy reduce birth weight and affect organ maturation, impacting fetal development.

Purpose of the Study:

• To review evidence on how antenatal glucocorticoid exposure affects offspring's long-term health.
• To explore the mechanisms of fetal programming related to glucocorticoids and the hypothalamic-pituitary-adrenal (HPA) axis.

Main Methods:

• Review of existing data from rodent and other animal models.
• Analysis of studies investigating the effects of endogenous and exogenous glucocorticoids during pregnancy.
• Examination of changes in offspring's birth weight, physiology, and behavior.

Main Results:

• Antenatal glucocorticoid exposure in animal models reduced offspring birth weight.
• Offspring exhibited permanent hypertension, hyperglycemia, hyperinsulinemia, altered behavior, and neuroendocrine responses.
• Key processes involved setting the hypothalamic-pituitary-adrenal (HPA) axis 'set point' and glucocorticoid receptor (GR) expression.

Conclusions:

• Antenatal glucocorticoid exposure is a significant factor in fetal programming, leading to long-term health issues in offspring.
• Altered HPA axis function and GR expression are critical mechanisms underlying these programming effects.
• HPA axis hyperreactivity in low birth weight humans may indicate early signs of fetal programming.