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Sex- and age-specific effects of nutrition in early gestation and early postnatal life on hypothalamo-pituitary-adrenal axis and sympathoadrenal function in adult sheep

Poore, K.R., Boullin, J.P., Cleal, J.K., Newman, J.P., Noakes, D.E., Hanson, M.A. and Green, L.R. (2010) Sex- and age-specific effects of nutrition in early gestation and early postnatal life on hypothalamo-pituitary-adrenal axis and sympathoadrenal function in adult sheep The Journal of Physiology, 588, (12), pp. 2219-2237. (doi:10.1113/jphysiol.2010.187682). (PMID:20421287).

Record type: Article


The early-life environment affects risk of later metabolic disease, including glucose intolerance, insulin resistance and obesity. Changes in hypothalamo-pituitary-adrenal (HPA) axis and sympathoadrenal function may underlie these disorders. To determine consequences of undernutrition in early gestation and/or immediately following weaning on HPA axis and sympathoadrenal function, 2- to 3-year-old Welsh Mountain ewes received 100% (C, n = 39) or 50% nutritional requirements (U, n = 41) from 1-31 days gestation, and 100% thereafter. From weaning (12 weeks) to 25 weeks of age, male and female offspring were then either fed ad libitum (CC, n = 22; UC, n = 19) or were undernourished (CU, n = 17; UU, n = 22) such that body weight was reduced to 85% of their individual target, based on a growth trajectory calculated from weights taken between birth and 12 weeks. From 25 weeks, ad libitum feeding was restored for all offspring. At 1.5 and 2.5 years, adrenocorticotropic hormone (ACTH) and cortisol concentrations were measured at baseline and in response to corticotropin-releasing factor (CRF) (0.5 microg kg(1)) plus arginine vasopressin (AVP) (0.1 microg kg(1)). At 2.5 years, HPA axis and sympathoadrenal (catecholamine) responses to a transport and isolation stress test were also measured. In females, post-weaning undernutrition reduced pituitary output (ACTH) but increased adrenocortical responsiveness (cortisol:ACTH area under curve) during CRF/AVP challenge at 1.5 years and increased adrenomedullary output (adrenaline) to stress at 2.5 years. In males, cortisol responses to stress at 2.5 years were reduced in those with slower growth rates from 12 to 25 weeks. Early gestation undernutrition was associated with increased adrenocortical output in 2.5-year-old females only. Pituitary and adrenal responses were also related to adult body composition. Thus, poor growth in the post-weaning period induced by nutrient restriction has sex- and age-specific effects on HPA and sympathoadrenal function. With altered glucose tolerance previously reported in this model, this may have long-term detrimental effects on metabolic homeostasis and cardiovascular function.

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e-pub ahead of print date: 14 June 2010
Published date: 15 June 2010
Organisations: Faculty of Medicine, Dev Origins of Health & Disease


Local EPrints ID: 73566
ISSN: 0022-3751
PURE UUID: b629fcc8-d916-4621-bbc2-116cedaba374
ORCID for K.R. Poore: ORCID iD
ORCID for L.R. Green: ORCID iD

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Date deposited: 10 Mar 2010
Last modified: 18 Jul 2017 23:49

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Author: K.R. Poore ORCID iD
Author: J.P. Boullin
Author: J.K. Cleal
Author: J.P. Newman
Author: D.E. Noakes
Author: M.A. Hanson
Author: L.R. Green ORCID iD

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