Maternal nutrient restriction (48 h) modifies brain corticosteroid receptor expression and endocrine function in the fetal guinea pig.
Modification of the fetal environment has been shown to program hypothalamo-pituitary-adrenal (HPA) development. Altered expression of brain corticosteroid receptors is thought to be central to this process. In the fetal guinea pig, rapid development of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) occurs in concert with rapid brain growth. Since nutrient availability has been associated with programming of endocrine function, we hypothesized that 48 h of maternal nutrient deprivation during rapid brain growth modifies the fetal endocrine environment and alters expression of GR and MR in the fetal brain. Pregnant guinea pigs were deprived of food (water available ad libitum) or fed normally on gestational days 50-51, and euthanized on gd52 (term=70 days). Nutrient deprivation caused intrauterine growth restriction (IUGR), though brain growth was protected. Fetal and maternal plasma cortisol was elevated in the deprived animals (p<0. 001), though plasma adrenocorticotrophin (ACTH) was only elevated in maternal blood. In deprived fetuses, plasma thyroxin levels were significantly (p<0.001) lower than control. GR mRNA levels were significantly decreased in the hypothalamic paraventricular nucleus (PVN; p<0.05) and CA1/2 (p<0.01) region of the hippocampus in female fetuses, and in the hippocampal CA1/2 in male fetuses (p<0.01). In contrast, MR mRNA levels were not changed by nutrient deprivation. In conclusion, 48 h of nutrient deprivation, activates the maternal, but not the fetal HPA axis, and decreases GR mRNA but not MR mRNA levels in the developing hypothalamus and limbic system. These developmental perturbations may have an important impact on the trajectory of corticosteroid receptor development and therefore central glucocorticoid feedback regulation.
Lingas
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Departments of Physiology and Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada.
Dean
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F
Matthews
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SG
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose; D005246:Feedback / Q000502:physiology; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000737:chemistry* / Q000196:embryology*; D017403:In Situ Hybridization; D008032:Limbic System / Q000737:chemistry / Q000196:embryology; D008297:Male; D010913:Pituitary-Adrenal System / Q000737:chemistry / Q000196:embryology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D013974:Thyroxine / Q000097:blood
D001786:Blood Glucose; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000324:Adrenocorticotropic Hormone; D013974:Thyroxine; D006854:Hydrocortisone