Endocrine Abstracts (2001) 2 P69

Prenatal maternal nutrient restriction and regulation of the hypothalamo-pituitary-adrenal (HPA) axis in adult offspring

SG Matthews & RI Lingas

Depts of Physiology and Obstetrics & Gynaecology, University of Toronto, Toronto, Ontario.

The prenatal environment has a major influence on development and function of endocrine systems throughout life. We have shown that a short period of maternal nutrient restriction (48h), at the time of maximal fetal brain growth in the guinea pig, permanently modifies HPA function throughout the life of the offspring. This effect is highly sex-specific; males exhibit decreased basal and activated pituitary-adrenal activity, while females exhibit elevated activity. In the present study, we hypothesized that modification of HPA function in guinea pig offspring whose mothers had been nutrient restricted results from altered central glucocorticoid feedback, and hypothalamic drive to the pituitary. Pregnant guinea pigs were nutrient restricted (NR) or fed-normally (C) on days 50 and 51 of gestation, after which they were all fed normally (birth=68 days). Animals delivered naturally and offspring were grown to adulthood. Adult offspring were euthanized at ~80 days. Glucocorticoid receptor (GR) mRNA and mineralocorticoid receptor (MR) mRNA were measured in the hippocampus by in situ hybridization. GR and CRH mRNA were measured in hypothalamic nuclei. Hippocampal MR mRNA levels were lower in female offspring born to NR mothers. In contrast, MR mRNA levels were higher in the hippocampi of males born to NR mothers. Hippocampal and hypothalamic GR mRNA and CRH mRNA levels were not different between prenatal treatment groups in males or females. In conclusion, a reduction in MR mRNA, as seen in the female NR offspring, is suggestive of decreased glucocorticoid feedback sensitivity, and this is consistent with increased pituitary-adrenal activity seen in these animals. In contrast, an increase in MR mRNA levels, as in the male NR offspring, is consistent with reduced adrenocortical activity. Together, these studies indicate that a short period of prenatal nutrient restriction permanently modifies the hippocampal MR system but not central GR systems. These changes likely modulate altered HPA activity in these animals.

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