title: 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.
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.
authors.affiliation: Institute of Developmental Sciences, Developmental Origins of Health and Disease Division, University of Southampton, Southampton, UK. kpoore@soton.ac.uk
authors.forename: Kirsten R
authors.initials: KR
authors.lastname: Poore
authors.forename: Julian P
authors.initials: JP
authors.lastname: Boullin
authors.forename: Jane K
authors.initials: JK
authors.lastname: Cleal
authors.forename: James P
authors.initials: JP
authors.lastname: Newman
authors.forename: David E
authors.initials: DE
authors.lastname: Noakes
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Green
mesh_terms: D000311:Adrenal Glands / Q000294:innervation* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000367:Age Factors; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D005260:Female; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D012737:Sex Factors; D012756:Sheep; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone; D004837:Epinephrine