Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function in juvenile guinea pigs

Area of Science:

• Neuroendocrinology
• Developmental Biology
• Stress Physiology

Background:

• Prenatal exposure to glucocorticoids can impact offspring neurodevelopment.
• Understanding these effects is crucial, especially in species with mature offspring at birth.
• The hypothalamo-pituitary-adrenal (HPA) axis is a key stress response system potentially affected by prenatal factors.

Purpose of the Study:

• To investigate the effects of repeated prenatal glucocorticoid administration on HPA axis function in juvenile guinea pigs.
• To determine if sex differences exist in the neurodevelopmental consequences of prenatal glucocorticoid exposure.
• To examine alterations in corticosteroid receptor and gene expression within the HPA axis.

Main Methods:

• Pregnant guinea pigs received betamethasone or vehicle injections during gestation.
• Juvenile offspring were assessed for HPA axis response to maternal separation.
• Gene expression of corticosteroid receptors, corticotrophin-releasing factor (CRF), pro-opiomelanocortin (POMC), and CYP17 in the pituitary, adrenal, hippocampus, and hypothalamus was analyzed.

Main Results:

• Prenatal glucocorticoid exposure abolished the HPA axis response to maternal separation in juvenile males.
• Female offspring showed no significant HPA response to separation, irrespective of prenatal treatment.
• Males exhibited increased pituitary POMC and CRF receptor mRNA and decreased adrenocortical CYP17 mRNA, indicating sex-specific alterations.

Conclusions:

• Repeated prenatal glucocorticoid exposure significantly influences HPA axis function and regulation in juvenile guinea pigs.
• The effects involve altered gene expression in the pituitary and adrenal cortex.
• Juvenile males are more vulnerable to the neurodevelopmental consequences of prenatal glucocorticoid exposure than females.