Hepatic glucocorticoid receptor expression in adult sheep following early gestational and / or postnatal undernutrition

Hollis, L., Anthony, F.W., Hanson, M.A. and Green, L.R. (2007) Hepatic glucocorticoid receptor expression in adult sheep following early gestational and / or postnatal undernutrition. Proceedings of the Physiological Society, 6 (PC4).

Abstract

In humans and animals environmental constraints during pre- and postnatal life result in phenotypic changes that can be associated with altered cardiovascular and metabolic disease risk in later life (Barker et al., 2002, Poore et al., 2006). The liver is a key organ in glucose and lipid metabolism and altered maternal diet or body composition are associated with changes in fetal liver blood flow (Haugen et al., 2005). Intrauterine challenges such as hypoxia alter blood flow to left and right lobes of the liver differentially. Maternal gestational low protein diet in rats alters adult hepatic gene expression with different effects between liver lobes (Zhang & Byrne, 2000). The glucocorticoid receptor (GR) is a gene associated with disturbances in cardiovascular and metabolic control. However the interaction between pre- and postnatal environments on hepatic GR is unknown. We investigated the effect of reduced early gestation maternal nutrition and/or early postnatal life undernutrition on the expression of GR in adult sheep liver. Welsh Mountain ewes received 100% (C, n=36) or 50 % of total nutrient requirements (U, n=39) from 1-31 days of gestation, and 100 % thereafter. Offspring were fed ad libitum (CC, n=20; UC, n=19) or to reduce body weight to 85 % of individual target weight from 12 to 25 weeks postnatal age and ad libitum thereafter (CU, n=17; UU, n=21). Each group contained approximately equal numbers of males and females and the ratio of twins to singletons was ~2:1. Offspring were sacrificed at 2.5 years, the livers were harvested and segments from the left and right lobes were frozen in liquid nitrogen. GR mRNA levels were measured by semi quantitative RT-PCR and normalized using the mean of three housekeeping genes (RPL19, ?Actin and GAPDH) selected by use of the geNormTM normalizing kit. All data were analysed by ANOVA. Early life nutrition had no effect on GR mRNA expression. GR mRNA expression was significantly higher in males than females (P<0.001). In both males and females the right liver lobe had higher GR mRNA expression than the left (P<0.001). In females, twins had a higher GR mRNA expression than singletons (P<0.05). We conclude that differences in GR expression between left and right lobes of the liver exist in adult sheep, although early gestation and/or postnatal nutrition did not affect these levels. Our finding of increased GR mRNA expression in males suggests that they may be more sensitive to the adverse effects of excess glucocorticoids.

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Contributors

Author: M.A. Hanson

Author: L.R. Green

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