Maternal nutrient restriction over the period of rapid placental growth (i.e. 30-80 days) with subsequent adequate nutrition up to term, results in newborn with larger kidneys which exhibit an increased abundance of glucocorticoid receptor mRNA but a decline in the levels of 11βHSD2 mRNA expression and activity (Whorwood et al. 2001). The resulting offspring exhibit lower resting blood pressure but an increased responsiveness to noradrenaline (Gopalakrishnan et al. 2001). The aim of this study was therefore to determine the longer term consequences beyond the neonatal period of maternal nutrient restriction (NR), between early to mid gestation, on enzyme activity of 11βHSD2 in the kidneys of juvenile sheep.
Ten Welsh Mountain ewes of similar body weight and fat distribution were individually housed from 28 days gestation. Four ewes were NR, these consumed 3.5 MJ of metabolizable energy (ME) per day (~60 % of ME requirements for maintenance and growth of the conceptus) until 80 d gestation, with six controls (C) consuming 6.8-7.5 MJ/day. After 80 d gestation, until term (147 d), all animals consumed 6.8-7.5 MJ/day, sufficient to fully meet their ME requirements. Lambs were delivered spontaneously and each ewe raised a single lamb that was weaned at 6 weeks of age. At 6 months of age all lambs were humanely killed to enable tissue sampling. The kidneys were weighed and snap frozen in liquid nitrogen for subsequent enzyme preparation. Results for weight are expressed as mean values and standard deviations. Enzyme activities were determined in kidney homogenates by means of a radiometric conversion assay which determines the rate of conversion of tritiated cortisol to tritiated cortisone. Enzyme activities were compared between groups using a Mann-Whitney U test.
Kidney weights (g) from juvenile lambs were comparable between groups, mean ± S.D., (C) 46 ± 6.5, (NR) 47.5 ± 4.7). Plasma cortisol concentrations (nmol/l) were also similar (C) 22 ± 4, (NR) 20 ± 5. 11βHSD2 enzyme activity, expressed as median and interquartile range, did not differ significantly between the diet regimes (C) 1.21 (0.12-1.39) pmol/min/mg protein; (NR) 0.69 (0.14-1.26) pmol/min/mg protein. The nutritional programming of attenuated kidney 11βHSD2 expression and activity in the newborn period does not appear to persist into young adulthood suggesting this is not the major mechanism for development of hypertension in adult life. It is possible that other biochemical changes in kidney function are important in this regard.
G Gopalakrishnan was supported by a British Heart Foundation studentship. This study was financially supported by the Nutricia Research Foundation.