Prenatal undernutrition decreases the sensitivity of the hypothalamo-pituitary-adrenal axis in rat, as revealed by subcutaneous and intra-paraventricular dexamethasone challenges

Prenatal undernutrition is known to disturb the hypothalamo-pituitary-adrenal (HPA) axis, possibly through the programming of decreased expression of hypothalamic and pituitary glucocorticoid receptors. To test this hypothesis, we examined the corticosterone response to moderate subcutaneous (100 μg/kg) and intra-paraventricular (50 pmol, bilaterally) dexamethasone (DEX) challenges in normal eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily, while mothers of eutrophic rats received the same diet ad libitum. At day 40 of postnatal life (i) undernourished rats showed increased plasma corticosterone concentration compared to normals; and (ii) subcutaneous and intra-paraventricular administrations of DEX led to reduced corticosterone levels in normal and undernourished animals, the effect of DEX (administered either peripherally or centrally) being significantly lower in the latter group. Results suggest that the low sensitivity of the HPA axis to DEX as well as the increased plasma corticosterone observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor underexpression found in the hypothalamus and pituitary of in utero undernourished animals, but alternative explanations involving central noradrenergic adaptive changes could also be possible.