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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

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
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 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.
0022-3751
2219-2237
Poore, K.R.
b9529ba3-6432-4935-b8fd-6e382f11f0ad
Boullin, J.P.
ba533803-491f-469a-a2ce-631fb14997cd
Cleal, J.K.
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Newman, J.P.
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Noakes, D.E.
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Hanson, M.A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Green, L.R.
8a601974-efe5-4916-9268-9e7bc72d89c5
Poore, K.R.
b9529ba3-6432-4935-b8fd-6e382f11f0ad
Boullin, J.P.
ba533803-491f-469a-a2ce-631fb14997cd
Cleal, J.K.
18cfd2c1-bd86-4a13-b38f-c321af56da66
Newman, J.P.
38b6cc7a-a882-40fd-a03a-388aae18416d
Noakes, D.E.
60ddcddc-7be2-40a0-b0b5-8d5a9326cbd2
Hanson, M.A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Green, L.R.
8a601974-efe5-4916-9268-9e7bc72d89c5

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. Journal of Physiology, 588 (12), 2219-2237. (doi:10.1113/jphysiol.2010.187682). (PMID:20421287)

Record type: Article

Abstract

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

Identifiers

Local EPrints ID: 73566
URI: http://eprints.soton.ac.uk/id/eprint/73566
ISSN: 0022-3751
PURE UUID: b629fcc8-d916-4621-bbc2-116cedaba374
ORCID for K.R. Poore: ORCID iD orcid.org/0000-0002-1455-0615
ORCID for J.K. Cleal: ORCID iD orcid.org/0000-0001-7978-4327
ORCID for M.A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for L.R. Green: ORCID iD orcid.org/0000-0001-7423-9696

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Date deposited: 10 Mar 2010
Last modified: 18 Feb 2021 16:59

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