Postnatal hypothalamic-pituitary-adrenal function in sheep is influenced by age and sex, but not by prenatal growth restriction

The relationship between impaired fetal nutrient supply and postnatal hypothalamic–pituitary–adrenal (HPA) function was examined in ovine models of prenatal growth restriction (GR) caused by small placental size (SP) or by maternal undernutrition (UN). Adrenocorticotrophin (ACTH) and cortisol responses following corticotrophin-releasing hormone (CRH) plus arginine vasopressin (AVP) challenge were examined at 9, 18 and 24 months in growth-restricted (GR-SP) and normal birthweight (control) females (Experiment 1), and at 6 months in growth-restricted (GR-SP, GR-UN) and normal weight males and females (Experiment 2). In Experiment 1, GR-SP offspring were born early, were 40% lighter at birth and had higher fractional weight gains to weaning than control offspring. Baseline ACTH and cortisol were independent of GR and cortisol decreased with age. GR did not affect the HPA response to CRH + AVP challenge at any stage, but ACTH increased with age. In Experiment 2, birthweight was greater in control offspring than in GR-UN offspring, which had a higher birthweight again compared with GR-SP offspring. Only the latter group was born early and exhibited rapid catch-up growth to weaning. Neither nutritional route to GR altered HPA function at 6 months. Males grew faster than females and HPA responses after stimulation were lower in males. Together, the results of these studies demonstrate that postnatal HPA function in sheep is influenced by age and sex, but not by GR.