Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring

被引:117
作者
Bloomfield, FH
Oliver, MH
Giannoulias, CD
Gluckman, PD
Harding, JE
Challis, JRG
机构
[1] Univ Auckland, Liggins Inst, Auckland 1, New Zealand
[2] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5S 1A8, Canada
[4] Canadian Inst Hlth Res Grp Fetal & Neonatal Hlth, Toronto, ON M5S 1A8, Canada
关键词
D O I
10.1210/en.2003-0189
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Reduced size at birth in humans has been associated with altered function of the hypothalamic-pituitary-adrenal (HPA) axis in childhood and adult life. Experimentally, maternal undernutrition has also been associated with altered fetal HPA function. However, the relationship between birth size, fetal nutrition, and adult pathophysiology is not clear. We recently have reported that glucose tolerance, blood pressure, and IGF-I levels in adult sheep were more closely associated with birth weight than with nutritional insult in late gestation or with current weight. Here, we report adult HPA function in the same group of animals. Pregnant ewes were severely undernourished for 10 d (UN10) or 20 d (UN20) from 105 d gestation ( term, 146 d), or were ad libitum-fed controls. At 30 months, female offspring were subjected to an insulin tolerance test and a CRH plus arginine vasopressin (AVP) challenge. UN20 lambs were lighter at birth, but there were no significant differences in weight at 30 months. Adult UN10 ewes had an increased ACTH response to both CRH +AVP challenge and insulin tolerance test, but no differences in cortisol response. UN10 ewes also demonstrated elevated 11-deoxycortisol concentrations, but lower progesterone concentrations, in response to CRH + AVP challenge. In contrast, the responses of UN20 ewes to these challenges were not different from ad libitum controls. Protein levels of P450(c17) and P450(11beta1) were not significantly different among groups. We conclude that brief maternal undernutrition for 10 d, but not 20 d, in late gestation alters HPA function in adult offspring. In contrast to our previous findings, these HPA effects are independent of birth weight and current weight, suggesting that different mechanisms may be involved in programming different physiological axes.
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页码:2933 / 2940
页数:8
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