McCance and Widdowson had suggested that the critical influence exerted by nutrition during fetal life would be upon hypothalamic function30. Edwards and colleagues have suggested that blood pressure might be critically determined through the maternal glucocorticoid axis45. In dams given low protein diets, the activity of placental 11 POH-steroid dehydrogenase was reduced by about one third, which would increase the likelihood of fetal over-exposure to maternal glucocorticoids46. The extent to which maternal glucocorticoids might directly contribute to programming fetal metabolism has been explored47. Maternal administration of metyrapone or matemal adrenalectomy during early pregnancy abolishes the effect ofmaternal low protein diets upon the blood pressure of offspring47-48. This provides direct evidence that part of the effect might be attributed to changes in the hypothalamo-pituitary-adrenal axis in the mother and/or the fetus. Further support comes from the observations that maternal low protein diets induce modulation of glucocorticoid sensitive enzymes in the fetal brain and liver47-49 There is differential regulation of glucocorticoid receptors in the brain, liver and aorta, and offspring of dams given 9% protein during pregnancy do not show a diurnal pattern of ACTH in blood, although diurnal changes in cortisol concentrations are maintained47-49.
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