Document Detail

Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring.
MedLine Citation:
PMID:  12810548     Owner:  NLM     Status:  MEDLINE    
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.
Frank H Bloomfield; Mark H Oliver; C Diana Giannoulias; Peter D Gluckman; Jane E Harding; John R G Challis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  144     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-17     Completed Date:  2003-07-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2933-40     Citation Subset:  AIM; IM    
Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
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MeSH Terms
Adrenocorticotropic Hormone / metabolism
Age Factors
Androstenedione / metabolism
Animals, Newborn
Birth Weight
Cortodoxone / metabolism
Gestational Age
Hydrocortisone / metabolism
Hypothalamo-Hypophyseal System / metabolism*,  physiopathology
Pituitary-Adrenal System / metabolism*,  physiopathology
Placental Insufficiency / metabolism*,  physiopathology
Progesterone / metabolism
Reg. No./Substance:
152-58-9/Cortodoxone; 50-23-7/Hydrocortisone; 57-83-0/Progesterone; 63-05-8/Androstenedione; 9002-60-2/Adrenocorticotropic Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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