Hawkins P, Steyn C, McGarrigle H H, Saito T, Ozaki T, Stratford L L, Noakes D E, Hanson M A
Departments of Obstetrics and Gynaecology, University College London, London WC1E 6HX, UK.
J Endocrinol. 1999 Dec;163(3):553-61. doi: 10.1677/joe.0.1630553.
The fetal hypothalamic-pituitary-adrenal (HPA) axis has numerous key roles in development. Epidemiological data have linked adverse prenatal nutrition with altered organ development and increased incidence of disease in adult life. We studied HPA axis development in resting and stimulated states in late gestation fetal sheep, following 15% reduction in maternal nutritional intake over the first 70 days of gestation (dGA). Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and response profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). At 126-128 dGA cortisol profiles were also determined following ACTH administration. Basal ACTH and cortisol concentrations were not different between C and R fetuses. In R fetuses, ACTH response to CRH+AVP was significantly smaller at 113-116 dGA (P<0.01), and cortisol responses were smaller at both 113-116 dGA (P<0.01) and 125-127 dGA (P<0.0001). Cortisol response to ACTH was also smaller in R fetuses (P<0.001). We conclude that, in late gestation fetal sheep, pituitary and adrenal responsiveness is reduced following modest maternal nutrient restriction in early gestation.
胎儿下丘脑 - 垂体 - 肾上腺（HPA）轴在发育过程中具有众多关键作用。流行病学数据表明，产前营养不良与器官发育改变以及成年后疾病发病率增加有关。我们研究了妊娠晚期胎羊在静息和刺激状态下的HPA轴发育情况，这些胎羊的母亲在妊娠的前70天（dGA）营养摄入量减少了15%。对来自对照（C）和营养受限（R）母羊的胎儿进行长期插管，并在给予促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）后，于113 - 116和125 - 127 dGA测定促肾上腺皮质激素（ACTH）和皮质醇的反应曲线。在126 - 128 dGA，给予ACTH后也测定了皮质醇曲线。C组和R组胎儿的基础ACTH和皮质醇浓度没有差异。在R组胎儿中，113 - 116 dGA时ACTH对CRH + AVP的反应显著较小（P<0.01），113 - 116 dGA（P<0.01）和125 - 127 dGA（P<0.0001）时皮质醇反应均较小。R组胎儿对ACTH的皮质醇反应也较小（P<0.001）。我们得出结论，在妊娠晚期胎羊中，妊娠早期母亲适度营养限制后，垂体和肾上腺的反应性降低。
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