Poore K R, Fowden A L
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
J Physiol. 2003 Feb 15;547(Pt 1):107-16. doi: 10.1113/jphysiol.2002.024349. Epub 2002 Nov 8.
Programming of the hypothalamo-pituitary-adrenal (HPA) axis during prenatal and early postnatal life may explain, in part, the association between low birth weight (BW) and the increased incidence of cardiovascular and metabolic disease in later life. This study examined the effect of natural variations in BW on HPA axis function in juvenile and adult pigs. Low (< 1.47 kg) and high (> 1.53 kg) BW pure-bred Large White piglets from 15 litters were studied at 3 (n = 47) and 12 (n = 17) months of age. At each age, HPA axis function was tested by hypoglycaemic challenge (I.V. insulin; 0.5 IU (kg body weight)(-1)) and ACTH challenge (I.V. Synacthen, 2 microg (kg body weight)(-1)). At 3 months of age, adrenal size, the ratio of adrenal cortical to medullary area and stimulated cortisol concentrations were elevated in pigs that were of low BW and that remained small after birth. At 12 months of age, thinness at birth was associated with elevated adrenal responsiveness to insulin-induced hypoglycaemia. These results are consistent with the hypothesis that impaired fetal and early postnatal growth are associated with altered HPA axis function in later life.
产前和产后早期下丘脑 - 垂体 - 肾上腺(HPA)轴的编程可能部分解释了低出生体重(BW)与晚年心血管和代谢疾病发病率增加之间的关联。本研究考察了BW的自然变化对幼年和成年猪HPA轴功能的影响。对来自15窝的低体重(<1.47千克)和高体重(>1.53千克)纯种大白仔猪在3个月(n = 47)和12个月(n = 17)龄时进行了研究。在每个年龄阶段,通过低血糖刺激(静脉注射胰岛素;0.5 IU(千克体重)⁻¹)和促肾上腺皮质激素刺激(静脉注射合成促肾上腺皮质激素,2微克(千克体重)⁻¹)来测试HPA轴功能。在3月龄时,低体重且出生后仍体型较小的猪的肾上腺大小、肾上腺皮质与髓质面积之比以及刺激后的皮质醇浓度均升高。在12月龄时,出生时体重较轻与肾上腺对胰岛素诱导的低血糖反应性升高有关。这些结果与以下假设一致,即胎儿期和出生后早期生长受损与晚年HPA轴功能改变有关。