Maternal protein restriction influences the programming of the rat hypothalamic-pituitary-adrenal axis.
The role of glucocorticoids in the intrauterine programming of hypertension was assessed in the progeny of rats fed either 18 g casein/100 g diet (control diet) or 9 g casein/100 g diet (low protein diet), before conception and throughout pregnancy. Rats exposed to the low protein diet had significantly (P < 0.05) higher systolic blood pressures than control animals, when weaned. These rats had elevated brain and liver activities of specific glucocorticoid-inducible marker enzymes, relative to controls. Glycerol 3-phosphate dehydrogenase activity was also higher (377%) in whole brains of newborn rats exposed to low protein diet in utero, but no similar effect of corticosteroids was noted in brains of d 20 fetuses. Weanling rats of the low protein group exhibited a blunted diurnal pattern of adrenocorticotrophin (ACTH) concentrations in plasma. Plasma corticosterone concentrations were unaltered by prenatal dietary experience and exhibited a normal pattern of diurnal variation. Brain regional 11beta-hydroxysteroid dehydrogenase activities were unaltered by prenatal dietary experience, as was binding of 3H-corticosterone to type I glucocorticoid receptors in hippocampus, hypothalamus and liver. Type II glucocorticoid receptor binding capacity and receptor numbers in male rats were apparently elevated in hippocampus of low protein-exposed rats and were significantly lower in liver (P < 0.05), relative to control rats. Programming of the hypothalamic-pituitary-adrenal axis is inferred, and the observation that binding of steroid to type II receptor sites in vascular tissue is increased in low protein exposed rats may provide a direct mechanism for modulation of blood pressure by glucocorticoids in this model.
Langley-Evans
S C
SC
Department of Human Nutrition, University of Southampton, United Kingdom.
Gardner
D S
DS
Jackson
A A
AA
D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000201:enzymology; D003345:Corticosterone / Q000097:blood; D018753:Diet, Protein-Restricted; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007031:Hypothalamus / Q000502:physiology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; D011770:Pyruvate Kinase; D005974:Glutamate-Ammonia Ligase; D003345:Corticosterone