Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat

Prenatal undernutrition induces a variety of cardiovascular alterations in mammals when adults, including hypertension and hypercortisolism, which are thought to be caused by decreased glucocorticoid feedback control of the hypothalamus-pituitary-adrenal (HPA) axis programmed during fetal life. Hypothalamic CRH seems to be involved in blood pressure elevation of spontaneously hypertensive rats and in primary hypertension of humans, but the influence of prenatal undernutrition on CRH expression has deserved little attention. Here, we studied the expression of both CRH mRNA and CRH protein in the hypothalamus of neonatal and juvenile offspring of rats undernourished during fetal life, as well as the plasma levels of CRH and corticosterone. Prenatal undernutrition of pups was induced by submitting pregnant rats to diet restriction (10 g daily of 21% protein standard laboratory diet). Pups born from dams with free access to the standard laboratory diet served as controls. At day 2 of postnatal age, undernourished pups showed lower body and brain weights, but higher plasma CRH and corticosterone than normal pups. At day 40 of age, brain weight was significantly decreased in the undernourished rats, while plasma corticosterone, plasma CRH and systolic pressure were significantly increased in these animals. At days 2 and 40 of postnatal age, increased CRH mRNA expression and CRH concentration were found in the hypothalamus of undernourished rats. Results indicate that, in the rat, prenatal undernutrition led to fetal programming of CRH overexpression, a neuropeptide serving as activating signal to the HPA axis and/or to extrahypothalamic brain regions concerned with cardiovascular regulation.