Laboratorio de Fisiología y Biofísica de Membranas, Facultad de Biología, Universidad de La Laguna, Tenerife, Spain.
J Neuroendocrinol. 2012 Feb;24(2):292-309. doi: 10.1111/j.1365-2826.2011.02242.x.
To determine the involvement of physiological doses of oestradiol on brain lipid composition, we have analysed the lipid class and fatty acid composition of phospholipids in the brain from pregnant and 17β-oestradiol-treated rats. Rats were randomly divided into three groups: ovariectomised control (OVX + VEH), ovariectomised oestradiol-treated (OVX + E(2) ) and pregnant (PREG) rats. Rats from the OVX + E(2) group were injected daily with different doses of 17β-oestradiol mimicking the plasma levels observed during pregnancy. Analyses of brain lipid class composition showed that physiological doses of oestradiol increased cholesterol levels of the OVX + E(2) group compared to the OVX + VEH group. It was also found that cholesterol levels in the PREG group were significantly lower than in the OVX + VEH and OVX + E(2) groups, indicating the involvement of gestational hormones other than oestradiol in the regulation of brain cholesterol during pregnancy. Brains from pregnant rats also exhibited reduced levels of plasmalogens and saturated fatty acids compared to the ovariectomised groups, especially in the second half of pregnancy. Interestingly, analyses of fatty acid composition of phospholipids revealed that physiological doses of oestradiol increased brain docosahexaenoic acid (DHA; 22:6 n-3) levels. Moreover, DHA levels in pregnant rats were similar to those observed in the OVX + E(2) group at all stages, suggesting that oestradiol is the main hormone in the regulation of brain DHA levels during pregnancy. Liver appears to be the major source for n-3 and n-6 long chain polyunsaturated fatty acids (LCPUFAs) DHA and arachidonic acid, which are released and transported to the maternal brain and the developing foetus under the influence of oestrogens. We also observed that the largest depots of n-3 and n-6 LCPUFA precursors (linolenic acid and linoleic acid, respectively) occur in adipose tissue triglycerides, which, in turn are significantly increased during pregnancy. Our observations are in accordance with an oestradiol-induced increased bioavailability of brain DHA in pregnant rats. We hypothesise that the reduction of maternal brain DHA observed at the end of pregnancy is a result of the very high demand DHA of foetal brain, which overcomes the maximal maternal (and likely foetal) capacity for de novo DHA synthesis in the liver and brain.
为了确定生理剂量的雌二醇对大脑脂质组成的影响，我们分析了来自怀孕和 17β-雌二醇处理的大鼠的脑磷脂的脂质类别和脂肪酸组成。大鼠被随机分为三组：卵巢切除对照（OVX+VEH）、卵巢切除雌二醇处理（OVX+E2）和怀孕（PREG）大鼠。OVX+E2 组的大鼠每天接受不同剂量的 17β-雌二醇注射，模拟怀孕期间观察到的血浆水平。脑脂质类别组成分析表明，生理剂量的雌二醇使 OVX+E2 组的胆固醇水平升高，与 OVX+VEH 组相比。还发现，PREG 组的胆固醇水平明显低于 OVX+VEH 和 OVX+E2 组，这表明妊娠期间除了雌二醇之外，还有其他妊娠激素参与了脑胆固醇的调节。与卵巢切除组相比，怀孕大鼠的脑还表现出更少的脑磷脂质和饱和脂肪酸，尤其是在怀孕的后半期。有趣的是，磷脂脂肪酸组成分析表明，生理剂量的雌二醇增加了大脑二十二碳六烯酸（DHA；22:6n-3）的水平。此外，在所有阶段，怀孕大鼠的 DHA 水平与 OVX+E2 组相似，这表明雌二醇是调节怀孕期间大脑 DHA 水平的主要激素。肝脏似乎是 n-3 和 n-6 长链多不饱和脂肪酸（LCPUFA）DHA 和花生四烯酸的主要来源，在雌激素的影响下，这些脂肪酸被释放并转运到母体大脑和发育中的胎儿。我们还观察到，n-3 和 n-6 LCPUFA 前体（亚麻酸和亚油酸）的最大储存库分别存在于脂肪组织甘油三酯中，而在怀孕期间，脂肪组织甘油三酯的含量显著增加。我们的观察结果与怀孕大鼠大脑中 DHA 的生物利用度增加与雌二醇有关。我们假设，在妊娠末期观察到的母体大脑 DHA 减少是由于胎儿大脑对 DHA 的极高需求所致，这超过了母体（可能还有胎儿）肝脏和大脑中新合成 DHA 的最大能力。
