Programming of the HPA axis during prenatal and early postnatal life may explain, in part, the association between low birth weight (BW) and the increased incidence of cardiovascular and metabolic disease in later life. The present study examined the effect of variations in intrauterine growth on HPA axis function, assessed by an insulin-induced hypoglycemic challenge, in 3 and 12 month (m) old pigs.
Low BW (<1.5 kg; n=22) and high BW (>1.5 kg; n=25) piglets were selected from 16 litters. At 3 and 12m, the pigs were tranquilised and catheters were inserted into the dorsal aorta and vena cava under general anaesthesia. After recovery, porcine insulin (0.5 IU/kg, iv) was given and 2ml arterial blood samples were taken for 2 hr for analysis of plasma ACTH and cortisol concentrations by RIA. Body and adrenal weights and the ratio of cortex:medulla area were measured at both ages.
ACTH and cortisol concentrations were significantly (P<0.001) elevated during hypoglycemia at 3 and 12m. At 3m, the cortisol but not the ACTH response to hypoglycaemia was significantly greater (P<0.05) in low than high BW pigs. The adrenal:body weight and cortical:medullary ratios were also significantly (P<0.05) greater in low than high BW pigs at 3m. In low BW pigs at 12m, the adrenal:body weight ratio was also reduced although the ratio of adrenal cortex:medulla and the ACTH and cortisol responses to hypoglycemia were similar to those in high BW pigs.
These results are consistent with the hypothesis that impaired fetal growth and low BW are associated with altered HPA axis function in later life. Supported by the Wellcome Trust.
03 - 04 Dec 2001
Society for Endocrinology