Department of Obstetrics and Gynecology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1062, USA.
Br J Nutr. 2012 Mar;107(5):665-73. doi: 10.1017/S0007114511003448. Epub 2011 Jul 26.
We previously reported that gestational dietary protein restriction in rats causes sex-related differences in development of blood pressure (BP) in the offspring, which is more pronounced in males than in females. As such effects may depend on sex hormones, we investigated the role of oestradiol in the development of hypertension in female offspring of protein-restricted dams. Female offspring of pregnant rats fed normal (20 %) or protein-restricted (6 %) casein diets throughout pregnancy were kept either intact, ovariectomised or ovariectomised with oestradiol supplementation. BP, Plasma oestradiol and testosterone levels, and vascular oestrogen receptor (ER) were examined. BP was significantly higher and plasma oestradiol levels were significantly lower ( - 34 %) in intact protein-restricted female offspring compared to corresponding controls. Further decrease in oestradiol levels by ovariectomy exacerbated hypertension in the protein-restricted females, with an earlier onset and more prominent elevation in BP compared to controls. Oestradiol supplementation in ovariectomised protein-restricted females significantly reversed ovariectomy-induced hypertension but did not normalise BP to control levels. The hypertensive protein-restricted females have reduced vascular ERα expression that was unaffected by ovariectomy or oestradiol replacement. In addition, testosterone levels were significantly higher by 2·4-, 3·4- and 2·8-fold in intact, ovariectomised and oestradiol-replaced protein-restricted females compared to corresponding controls. The present data show that: (1) hypertension in protein-restricted adult female offspring is associated with reduced plasma oestradiol levels; (2) oestradiol protects and limits the severity of hypertension in protein-restricted females and contributes to sexual dimorphism; (3) oestradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ERα receptors and/or increased circulating testosterone levels.
我们之前曾报道过，在大鼠中，妊娠期饮食蛋白质限制会导致后代的血压（BP）发育出现性别相关差异，且雄性比雌性更为明显。由于这些影响可能依赖于性激素，我们研究了雌激素在蛋白质限制的母鼠后代雌性子代表高血压发展中的作用。整个妊娠期给予正常（20%）或蛋白质限制（6%）酪蛋白饮食的怀孕大鼠的雌性后代，要么保持完整，要么卵巢切除术，要么卵巢切除术并补充雌激素。检查血压、血浆雌激素和睾丸激素水平以及血管雌激素受体（ER）。与相应的对照组相比，完整的蛋白质限制雌性后代的血压明显升高，血浆雌激素水平明显降低（-34%）。卵巢切除术进一步降低雌激素水平会加剧蛋白质限制雌性的高血压，与对照组相比，其血压的起始时间更早，升高幅度更大。在卵巢切除的蛋白质限制雌性中补充雌激素可显著逆转卵巢切除引起的高血压，但不能使血压恢复到对照水平。高血压的蛋白质限制雌性的血管 ERα 表达减少，而卵巢切除术或雌激素替代对其没有影响。此外，与相应的对照组相比，完整的、卵巢切除术的和雌激素替代的蛋白质限制雌性的睾丸激素水平分别高出 2.4 倍、3.4 倍和 2.8 倍。本数据表明：（1）蛋白质限制成年雌性后代的高血压与血浆雌激素水平降低有关；（2）雌激素可保护和限制蛋白质限制雌性的高血压严重程度，并促进性别二态性；（3）雌激素替代不能完全逆转高血压，这可能与血管 ERα 受体的有限可用性和/或循环睾丸激素水平增加有关。
