Reduced size at birth in humans has been associated with altered function of the hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life. Experimentally, maternal undernutrition has also been associated with altered fetal HPA function. However the relationship between birth size, fetal nutrition and adult pathophysiology is not clear. We recently have reported that glucose tolerance, blood pressure and IGF-I levels in adult sheep were more closely associated with birth weight than with nutritional insult in late gestation or with current weight. Here we report adult HPA function in the same group of animals.

Pregnant ewes were severely undernourished for 10 (UN10) or 20 (UN20) days from 105 d gestation (term = 146 d), or were ad libitum-fed controls. At 30 months female offspring were subjected to an insulin tolerance test (ITT) and a corticotrophin releasing hormone (CRH) + arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth but there were no significant differences in weight at 30 months. Adult UN10 ewes had an increased adrenocorticotrophin (ACTH) response to both CRH+AVP challenge and ITT, but no differences in cortisol response. UN10 ewes also demonstrated elevated 11-deoxycortisol concentrations, but lower progesterone concentrations, in response to CRH+AVP challenge. In contrast, the responses of UN20 ewes to these challenges were not different from ad libitum controls. Protein levels of P450_c17 and P450₁₁₁ were not significantly different among groups.

We conclude that brief maternal undernutrition for 10 days, but not 20 days, in late gestation alters HPA function in adult offspring. In contrast to our previous findings, these HPA effects are independent of birthweight and current weight, suggesting that different mechanisms may be involved in programing different physiologic axes.