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Maternal protein restriction influences the programming of the rat hypothalamic-pituitary-adrenal axis
S C Langley-Evans1, D S Gardner, A A Jackson
1Department of Human Nutrition, University of Southampton, United Kingdom.
Insights
Maternal low protein diet in rats programs offspring for hypertension. This is linked to altered glucocorticoid signaling and programming of the hypothalamic-pituitary-adrenal axis.
Area of Science:
- Endocrinology
- Developmental Biology
- Nutritional Science
Background:
- Intrauterine programming influences long-term health outcomes.
- Glucocorticoids play a critical role in stress response and metabolism.
- Hypertension is a complex condition with potential developmental origins.
Purpose of the Study:
- To investigate the role of glucocorticoids in intrauterine programming of hypertension.
- To assess the impact of maternal low protein diet on offspring blood pressure and related molecular markers.
Main Methods:
- Rats were fed control or low protein diets before and during pregnancy.
- Systolic blood pressure, enzyme activities, and hormone concentrations were measured in offspring.
- Glucocorticoid receptor binding was analyzed in various tissues.
Main Results:
- Offspring from low protein diet dams exhibited higher systolic blood pressure.
- Elevated brain and liver glucocorticoid-inducible enzyme activities were observed.
- Alterations in adrenocorticotrophin (ACTH) patterns and type II glucocorticoid receptor binding were noted.
Conclusions:
- Prenatal exposure to a low protein diet can program hypertension in offspring.
- Glucocorticoid signaling pathways, including the hypothalamic-pituitary-adrenal axis, are implicated.
- Altered glucocorticoid receptor binding may represent a direct mechanism for blood pressure modulation.
Abstract:
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.