Prenatal Dexamethasone Exposure Induces Changes in Nonhuman Primate Offspring Cardiometabolic and Hypothalamic-pituitary-adrenal Axis Function.
From: Endocrinology Unit, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, United Kingdom.
The Journal of clinical investigation
- Publish Date: Apr 2007
- ISSN: 0021-9738
- Volume: 117
- Issue: 4
- Pages: 1058-67
- Medium: Print
- Language: English
- Citation (JAMA): de Vries Annick, Holmes Megan C, Heijnis Areke, et al. Prenatal Dexamethasone Exposure Induces Changes in Nonhuman Primate Offspring Cardiometabolic and Hypothalamic-pituitary-adrenal Axis Function.. J. Clin. Invest. Apr 2007;117:1058-67
Abstract
Prenatal stress or glucocorticoid administration has persisting “programming” effects on offspring in rodents and other model species. Multiple doses of glucocorticoids are in widespread use in obstetric practice. To examine the clinical relevance of glucocorticoid programming, we gave 50, 120, or 200 microg/kg/d of dexamethasone (dex50, dex120, or dex200) orally from mid-term to a singleton-bearing nonhuman primate, Chlorocebus aethiops (African vervet). Dexamethasone dose-dependently reduced maternal cortisol levels without effecting maternal blood pressure, glucose, electrolytes, or weight gain. Birth weight was unaffected by any dexamethasone dose, although postnatal growth was attenuated after dex120 and dex200. At 8 months of age, dex120 and dex200 offspring showed impaired glucose tolerance and hyperinsulinemia, with reduced (approximately 25%) pancreatic beta cell number at 12 months. Dex120 and dex200 offspring had increased systolic and diastolic blood pressures at 12 months. Mild stress produced an exaggerated cortisol response in dex200 offspring, implying hypothalamic-pituitary-adrenal axis programming. The data are compatible with the extrapolation of the glucocorticoid programming hypothesis to primates and indicate that repeated glucocorticoid therapy and perhaps chronic stress in humans may have long-term effects.
Mesh Headings (Keywords): Animals, Cercopithecus aethiops, Dexamethasone, Female, Heart, Hypothalamo-Hypophyseal System, Models, Animal, Myocardium, Pregnancy, Prenatal Exposure Delayed Effects
Check for Full Text / PubMed Unique Identifier (PMID): 17380204
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