首页> 美国卫生研究院文献>The Journal of Physiology >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
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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

机译:妊娠早期和产后早期营养对成年绵羊下丘脑-垂体-肾上腺轴和交感肾上腺功能的性别和年龄影响

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摘要

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 μg kg−1) plus arginine vasopressin (AVP) (0.1 μg 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.
机译:早期生活环境会影响后期代谢疾病的风险,包括葡萄糖耐受不良,胰岛素抵抗和肥胖症。下丘脑-垂体-肾上腺(HPA)轴和交感肾上腺功能的改变可能是这些疾病的基础。为了确定早孕和/或断奶后HPA轴和交感肾上腺功能不良的营养不良后果,对2至3岁的威尔士山母羊提供100%(C,n = 39)或50%的营养需求(U, n = 41),从妊娠1–31天开始,此后100%。从断奶(12周)到25周龄,雄性和雌性后代被随意喂养(CC,n = 22; UC,n = 19)或营养不良(CU,n = 17; UU,n = 22) ),以根据从出生到12周之间的体重计算出的生长轨迹,将体重降低到其各自目标的85%。从25周起,所有后代恢复了自由采食。在1.5和2.5岁时,测量基线时的肾上腺皮质激素(ACTH)和皮质醇浓度,并响应促肾上腺皮质激素释放因子(CRF)(0.5μgkg -1 )加精氨酸升压素(AVP)( 0.1μg千克 -1 )。在2.5年时,还测量了HPA轴和交感肾上腺(儿茶酚胺)对运输和孤立压力测试的反应。在女性中,断奶后营养不良降低了垂体输出量(ACTH),但在1.5年的CRF / AVP挑战期间增加了肾上腺皮质反应性(皮质醇:ACTH曲线下面积),并在2.5年时增加了对应激的肾上腺皮质输出量(肾上腺素)。在男性中,皮质醇在2.5岁时对压力的反应在生长速度从12周降低至25周的患者中降低了。早期妊娠营养不良仅与2.5岁女性的肾上腺皮质输出量增加有关。垂体和肾上腺的反应也与成人的身体组成有关。因此,由营养限制引起的断奶后生长不良对HPA和交感肾上腺功能有性别和年龄特异性影响。先前在该模型中报道过葡萄糖耐量的改变,这可能对代谢稳态和心血管功能产生长期有害影响。

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