School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia 5000, Australia.
Reproduction. 2013 Oct 1;146(5):443-54. doi: 10.1530/REP-13-0219. Print 2013.
Exposure to dietary restriction during the periconceptional period in either normal or obese ewes results in increased adrenal growth and a greater cortisol response to stress in the offspring, but the mechanisms that programme these changes are not fully understood. Activation of the angiotensin type 1 receptor (AT1R) has been demonstrated to stimulate adrenal growth and steroidogenesis. We have used an embryo transfer model in the sheep to investigate the effects of exposure to dietary restriction in normal or obese mothers from before and 1 week after conception on the methylation status, expression, abundance and localisation of key components of the renin-angiotensin system (RAS) in the adrenal of post-natal lambs. Maternal dietary restriction in normal or obese ewes during the periconceptional period resulted in an increase in angiotensin-converting enzyme (ACE) and AT1R abundance in the absence of changes in the methylation status or mRNA expression of ACE and AT1R in the adrenal of the offspring. Exposure to maternal obesity alone also resulted in an increase in adrenal AT1R abundance. There was no effect of maternal dietary restriction or obesity on ACE2 and AT2R or on ERK, calcium/calmodulin-dependent kinase II abundance, and their phosphorylated forms in the lamb adrenal. Thus, weight loss around the time of conception, in both normal-weight and obese ewes, results in changes within the intra-adrenal RAS consistent with increased AT1R activation. These changes within the intra-adrenal RAS system may contribute to the greater adrenal stress response following exposure to signals of adversity in the periconceptional period.
在正常或肥胖母羊的围孕期限制饮食会导致后代的肾上腺生长增加和对压力的皮质醇反应增强，但调节这些变化的机制尚未完全了解。血管紧张素 1 型受体 (AT1R) 的激活已被证明可刺激肾上腺生长和类固醇生成。我们使用绵羊胚胎转移模型研究了在正常或肥胖母亲在受孕前和受孕后 1 周接触饮食限制对产后羔羊肾上腺中肾素-血管紧张素系统 (RAS) 的关键成分的甲基化状态、表达、丰度和定位的影响。正常或肥胖母羊在围孕期的饮食限制导致 ACE（血管紧张素转换酶）和 AT1R 的丰度增加，而 ACE 和 AT1R 的甲基化状态或 mRNA 表达在后代的肾上腺中没有变化。单独暴露于母体肥胖也导致肾上腺 AT1R 的丰度增加。母羊饮食限制或肥胖对 ACE2 和 AT2R 或 ERK、钙/钙调蛋白依赖性激酶 II 的丰度及其在羔羊肾上腺中的磷酸化形式没有影响。因此，在正常体重和肥胖母羊中，受孕前后的体重减轻会导致肾上腺内 RAS 发生变化，与 AT1R 激活增加一致。围孕期逆境信号暴露后，肾上腺内 RAS 系统的这些变化可能导致更大的肾上腺应激反应。
