Hyatt Melanie A, Walker David A, Stephenson Terence, Symonds Michael E
Centre for Reproduction and Early Life, Institute of Clinical Research and Children's Brain Tumour Research Centre, University Hospital, Nottingham NG7 2UH, UK.
Proc Nutr Soc. 2004 Feb;63(1):127-35. doi: 10.1079/PNS2003324.
The somatotrophic axis is the main endocrine system regulating postnatal growth; however, prenatal growth is independent of growth hormone (GH). Fetal development relies on the coordinated actions of a range of hormones, including insulin-like growth factors (IGF), and prolactin (PRL), in the control of differentiation, growth and maturation. In the sheep the abundance peaks for liver IGF-II and PRL receptors occur during late gestation while that for IGF-I receptor occurs at birth. All receptors, with the exception of GH receptor subsequently decrease by age 6 months. It has been proposed that maternal undernutrition during gestation regulates the maturation of the fetal hypothalmic-pituitary-adrenal axis and endocrine sensitivity. Critically, the timing of the nutritional insult may affect the magnitude of reprogramming. Maternal malnutrition during early to mid-gestation (3.2-3.8 MJ/d (60% total metabolisable energy requirements) v. 8.7-9.9 MJ/d (150% total metabolisable energy requirements) between 28 and 80 d of gestation) had no effect on body or liver weight. Nutrient-restricted (NR) fetuses sampled at 80 d (mid-gestation) showed up-regulation of hepatic PRL receptor, but following refeeding the normal gestational rise in PRL and GH receptors did not occur. Hepatic IGF-II receptor was down regulated in NR fetuses at both mid- and late gestation. Conversely, 6-month-old offspring showed no difference in the abundance of either GH receptor or PRL receptor, while IGF-II mRNA was increased. Offspring of ewes malnourished during late gestation (9.1 MJ/d (60% total metabolisable energy requirements) v. 12.7 MJ/d (100% total metabolisable energy requirements) from 110 d of gestation to term) showed reduced abundance of hepatic GH and PRL receptor mRNA. In conclusion, maternal undernutrition during the various stages of gestation reprogrammed the PRL-GH-IGF axis. Nutritional regulation of cytokine receptors may contribute to altered liver function following the onset of GH-dependent growth, which may be important in regulating endocrine adaptations during subsequent periods of nutritional deprivation.
生长激素轴是调节出生后生长的主要内分泌系统；然而，产前生长独立于生长激素（GH）。胎儿发育依赖于一系列激素的协同作用，包括胰岛素样生长因子（IGF）和催乳素（PRL），以控制分化、生长和成熟。在绵羊中，肝脏IGF-II和PRL受体的丰度峰值出现在妊娠后期，而IGF-I受体的峰值出现在出生时。除了GH受体外，所有受体在6个月龄时随后都会减少。有人提出，孕期母体营养不良会调节胎儿下丘脑-垂体-肾上腺轴的成熟和内分泌敏感性。至关重要的是，营养损伤的时间可能会影响重编程的程度。妊娠早期至中期（妊娠28至80天期间，3.2 - 3.8 MJ/d（占总可代谢能量需求的60%）对8.7 - 9.9 MJ/d（占总可代谢能量需求的150%））母体营养不良对体重或肝脏重量没有影响。在妊娠80天（妊娠中期）取样的营养受限（NR）胎儿显示肝脏PRL受体上调，但重新喂食后，PRL和GH受体未出现正常的妊娠升高。在妊娠中期和晚期，NR胎儿的肝脏IGF-II受体下调。相反，6月龄的后代在GH受体或PRL受体的丰度上没有差异，而IGF-II mRNA增加。妊娠后期（妊娠110天至足月，9.1 MJ/d（占总可代谢能量需求的60%）对12.7 MJ/d（占总可代谢能量需求的100%））营养不良的母羊所产后代，肝脏GH和PRL受体mRNA的丰度降低。总之，孕期不同阶段的母体营养不良会对PRL - GH - IGF轴进行重编程。细胞因子受体的营养调节可能导致GH依赖生长开始后肝功能改变，这在调节随后营养剥夺期的内分泌适应中可能很重要。
