de Rooij Susanne R, Painter Rebecca C, Phillips David I W, Osmond Clive, Michels Robert P J, Bossuyt Patrick M M, Bleker Otto P, Roseboom Tessa J
Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, 1100DD Amsterdam, The Netherlands.
Eur J Endocrinol. 2006 Jul;155(1):153-60. doi: 10.1530/eje.1.02193.
The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis.
We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine.
Cortisol profiles after dexamethasone suppression and ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12)) differed between exposed and unexposed participants.
Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.
下丘脑 - 垂体 - 肾上腺（HPA）轴被认为易受胎儿编程影响，即不良的胎儿环境引发永久性生理和代谢改变，使个体在成年后易患疾病的过程。据推测，胎儿暴露于不良环境会改变HPA轴的设定点，导致HPA轴活性增加以及随后皮质醇浓度升高。在本研究中，我们检验了以下假设：孕期不同阶段暴露于饥荒与HPA轴活性增加有关。
我们对从荷兰饥荒出生队列中随机抽取的98名男性和女性进行了地塞米松抑制试验和促肾上腺皮质激素1 - 24刺激试验后，评估了血浆皮质醇浓度。队列成员为1944 - 1945年荷兰饥荒期间足月出生的单胎婴儿。
在妊娠晚期、中期或早期暴露于饥荒的参与者，地塞米松抑制试验和促肾上腺皮质激素1 - 24刺激试验后的皮质醇曲线相似（P = 0.78）。地塞米松抑制试验后，宫内暴露于饥荒者与未暴露者的皮质醇浓度无差异（平均差异 - 2%（95%置信区间（CI） - 27至23））。促肾上腺皮质激素1 - 24注射后，暴露组和未暴露组的皮质醇峰值浓度（20 nmol/l（95% CI - 27至66））、皮质醇增量（ - 5 nmol/l（95% CI -
56至47））或皮质醇曲线下面积（4%（95% CI - 4至12））均无差异。
产前饥荒暴露似乎不会影响成年期的HPA轴活性，至少在肾上腺水平不会。但这并不排除海马体和下丘脑水平的HPA轴活性改变。
