Reynolds Rebecca M, Walker Brian R, Syddall Holly E, Andrew Ruth, Wood Peter J, Phillips David I W
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Eur J Endocrinol. 2005 Feb;152(2):249-53. doi: 10.1530/eje.1.01846.
Increased hypothalamic-pituitary-adrenal (HPA) axis activity in men of low birthweight may be an important link between early life and the adult metabolic syndrome. In animal models females are more sensitive than males to HPA axis programming, but whether gender influences susceptibility in humans is unknown.
Birth cohort study.
We studied 106 women aged 67-78 years, from Hertfordshire, UK, in whom birthweight was recorded. Negative feedback sensitivity was assessed by an overnight low-dose (0.25 mg) dexa-methasone suppression test, and adrenal sensitivity by a low-dose (1 microg) ACTH(1 - 24) stimulation test. Cortisol and its metabolites were analysed in a 24 h urine collection. Data were compared with previously published identical measurements in 205 men aged 66-77 years from the same cohort.
In women, plasma cortisol levels after dexamethasone were lower (P < 0.0001) and peak cortisol following ACTH(1 - 24) were higher (P < 0.0001) than in men, suggesting a more responsive HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH(1 - 24) (P = 0.05 for trend) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from that in men; a 1 lb decrease in birthweight was associated with an incremental rise in cortisol of 12.6 nmol/l (95% confidence interval (CI) 1.4, 23.8) in men, P = 0.03, and 14.8 nmol/l (95% CI -0.4, 29.9) in women, P = 0.05 (P = 0.82 for birthweight x gender interaction). In a combined analysis of men and women adjusted for gender (n = 302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) greater incremental rise in plasma cortisol, P = 0.003.
Associations between lower birthweight and increased HPA axis activity are similar in men and women, supporting the hypothesis that HPA axis activation is an important mechanism underlying programming of adult disease.
低出生体重男性下丘脑 - 垂体 - 肾上腺（HPA）轴活性增加可能是早年生活与成人代谢综合征之间的重要联系。在动物模型中，雌性比雄性对HPA轴编程更敏感，但性别是否影响人类的易感性尚不清楚。
出生队列研究。
我们研究了来自英国赫特福德郡的106名67 - 78岁的女性，她们的出生体重有记录。通过过夜低剂量（0.25mg）地塞米松抑制试验评估负反馈敏感性，通过低剂量（1μg）促肾上腺皮质激素（ACTH）（1 - 24）刺激试验评估肾上腺敏感性。在24小时尿液收集样本中分析皮质醇及其代谢产物。将数据与之前发表的来自同一队列的205名66 - 77岁男性的相同测量结果进行比较。
与男性相比，女性在地塞米松后的血浆皮质醇水平较低（P < 0.0001），而在ACTH（1 - 24）刺激后的皮质醇峰值较高（P < 0.0001），表明HPA轴反应性更强。与男性一样，出生体重较低的女性对ACTH（1 - 24）的血浆皮质醇反应增强（趋势P = 0.05），但在地塞米松后的血浆皮质醇或尿皮质醇代谢产物排泄方面没有差异。女性中这种关联的强度与男性没有差异；出生体重每降低1磅，男性皮质醇增加12.6nmol/l（95%置信区间（CI）1.4，23.8），P = 0.03，女性增加14.8nmol/l（95%CI -0.4，29.9），P = 0.05（出生体重×性别交互作用P = 0.82）。在对性别进行校正的男性和女性的合并分析中（n = 302），出生体重每降低1磅，血浆皮质醇增量增加13.4nmol/l（95%CI 4.5，22.4），P = 0.003。
低出生体重与HPA轴活性增加之间的关联在男性和女性中相似，支持HPA轴激活是成人疾病编程基础的重要机制这一假设。
