Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep

Adverse environmental conditions before birth are known to program adult metabolic and endocrine phenotype in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared to saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline treated group. The results show that cortisol overexposure before birth programs pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges

Roll Back Malaria: a failing global health challenge: Developing a market for bed nets and insecticides is problematic

Low birth weight is associated with altered adipose tissue deposition and regulation of leptin production. This study determined the effects of naturally occurring variations in birth weight in pigs on postnatal growth patterns, body fat depth and plasma leptin and other hormone concentrations. Low (< 1.47 kg) and high (> 1.53 kg) birth weight piglets were studied at 3 months (juvenile; n= 47) and 12 months of age (young adult; n= 17). At each age, arterial and venous catheters were inserted under general anaesthesia. Plasma leptin, cortisol, glucose, insulin and catecholamine concentrations were determined in basal blood samples. Body fat depth was measured by ultrasound at 12 months of age. Overall, adult fat depth was greater in low compared to high birth weight pigs and increased fat depth was associated with thinness at birth and poor early growth rates. These effects were strongest in females. Fat depth was related to current weight only in males. Compared to high birth weight pigs, plasma leptin concentrations were reduced in low birth weight females at 3 months and in low birth weight males at 12 months of age. This study demonstrates sex-specific effects of low birth weight on postnatal growth and body fatness and on plasma leptin concentrations in pigs

Insulin sensitivity in juvenile and adult large white pigs of low and high birthweight

Aims/hypothesis We have previously demonstrated poor glucose tolerance in adult pigs of naturally occurring low birthweight. The aim of this study was to examine sensitivity to insulin in juvenile (3-month-old) and adult (12-month-old) pigs of low and high birthweight.Methods Low (<1.47 kg) and high (>1.53 kg) birthweight piglets from 15 litters were studied at 3 (n=47) and 12 (n=17) months of age. At each age the selected pigs were tranquilised and catheters were inserted into the dorsal aorta and caudal vena cava under general anaesthesia. After recovery, insulin sensitivity was measured as the glucose decrement (mmol·l–1·min–1) during the first 10 min after an intravenous insulin bolus (0.5 IU/kg). Data (means ± SEM) were analysed by the Student's t test, ANOVA and linear regression.Results The body weight of low birthweight female, but not male, pigs remained smaller than that of high birthweight pigs at 3 and 12 months of age. At 3 months, thinness at birth and rapid catch-up growth in the first month of life were associated with increased insulin sensitivity in males. In females thinness at 3 months was associated with reduced sensitivity to insulin. At 12 months, early postnatal catch-up growth was associated with insulin resistance, irrespective of sex, when all data were combined.Conclusions/interpretation The glucose intolerance previously observed in young adult pigs of low birthweight is probably due to insulin resistance. Early catch-up growth in low birthweight pigs was the clearest predictor of adult insulin resistance

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

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 µg (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

Prostaglandins in the foetal pig and prepartum endocrine changes in mother and foetus

Chronically catheterized sows and their foetuses were used to investigate the changes in steroids and prostaglandins in maternal and foetal plasma and in allantoic fluid before and during parturition. A rise in foetal plasma corticosteroid concentration began 5-7 days before delivery. This was accompanied by a rise in oestrogen levels in foetal and maternal plasma and in allantoic fluid. There were a significant venous-arterial differences in oestrogen across both uterine and umbilical circulations. A more gradual decrease in maternal plasma progesterone levels occurred with a pronounced fall 24 hr before parturition; wide arterio-venous (uterine) and venous-arterial (umbilical) progesterone differences were found. Prostaglandin concentrations remained low in the maternal circulation until the day of farrowing, when PGF and its metabolic 13, 14-dihydro-15-oxo prostaglandin (PGFM) rose 10-20 fold. Foetal plasma levels of PGF, PGF and PGFM were higher than those of the sow in the prepartum period, while allantoic fluid concentrations were even greater. A delivery, PGE and PGF in the umbilical vein and allantoic fluid were raised but in the arterial plasma of the piglets at birth only PGFM levels were high. There was a close correlation between the neonatal PGFM levels and those in maternal arterial plasma at the time of delivery