The effect of birth weight on hypothalamo-pituitary-adrenal axis function in juvenile and adult pigs

Abstract

Programming of the hypothalamo-pituitary-adrenal (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. This study examined the effect of natural variations in BW on HPA axis function in juvenile and adult pigs. Low (< 1.47 kg) and high (> 1.53 kg) BW pure-bred Large White piglets from 15 litters were studied at 3 (n = 47) and 12 (n = 17) months of age. At each age, HPA axis function was tested by hypoglycaemic challenge (I.V. insulin; 0.5 IU (kg body weight)(-1)) and ACTH challenge (I.V. Synacthen, 2 microg (kg body weight)(-1)). At 3 months of age, adrenal size, the ratio of adrenal cortical to medullary area and stimulated cortisol concentrations were elevated in pigs that were of low BW and that remained small after birth. At 12 months of age, thinness at birth was associated with elevated adrenal responsiveness to insulin-induced hypoglycaemia. These results are consistent with the hypothesis that impaired fetal and early postnatal growth are associated with altered HPA axis function in later life.

Figure 1. Adrenal size and morphometry in juvenile and adult pigs

The ratios of adrenal weight:current weight (CW) and cortical:medullary area in low (L; ▪) and high (H; □) BW pigs at 3 and 12 months of age. At 3 months of age, adrenal:CW (P < 0.01) and cortex:medulla ratios (P < 0.05) in low BW pigs were significantly greater than in high BW pigs, as indicated by asterisks.

Figure 2. Basal plasma ACTH, cortisol and catecholamine concentrations

Basal plasma ACTH (A), cortisol (B), noradrenaline (C) and adrenaline (D) concentrations in low (L; ▪) and high (H; □) BW pigs at 3 and 12 months of age. * Different effect of BW in male and female pigs: refer to text.

Figure 3. Plasma glucose, ACTH, cortisol and catecholamine concentrations during insulin challenge

Plasma glucose (A and F), ACTH (B and G), cortisol (C and H), noradrenaline (D and I) and adrenaline (E and J) concentrations in low (•) and high (○) BW pigs prior to and following insulin administration (0.5 IU (kg body weight)⁻¹; i.v.) at time 0 min (arrows) at 3 (A-E) and 12 (F-J) months of age. At 3 months of age, cortisol concentrations during insulin challenge in low BW pigs were significantly (P < 0.005) greater than in high BW pigs (* 2-way ANOVA). At 12 months of age, noradrenaline concentrations during insulin challenge in low BW pigs were significantly (P < 0.05) lower than in high BW pigs (* 2-way ANOVA).

Figure 4. Plasma cortisol concentrations during ACTH challenge

Plasma cortisol concentrations in low (•) and high (○) BW pigs prior to and following ACTH administration (2.0 µg (kg body weight)⁻¹; i.v.) at time 0 min (arrow) at 3 (A) and 12 (B) months of age. At 3 months of age, cortisol concentrations in low BW pigs were significantly (P < 0.005) greater than in high BW pigs (* 2-way ANOVA).