Faculty of Medicine, Department of Physiology, Hacettepe University, TR-06100, Ankara, Turkey.
Faculty of Medicine, Department of Nuclear Medicine, Hacettepe University, TR-06100, Ankara, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Aug;390(8):827-838. doi: 10.1007/s00210-017-1383-2. Epub 2017 May 29.
Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3 g/L) or high (0.8 g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.
睾酮、雌二醇和二氢睾酮是主要的性激素，负责在早期发育过程中组织和性分化大脑结构。下丘脑-垂体-肾上腺皮质轴、肾上腺细胞和性腺在性激素的产生中发挥着关键作用，并表达腺苷受体。咖啡因是一种非选择性的腺苷拮抗剂；因此，它可以调节这些组织中的代谢途径。此外，约 60%的孕妇会摄入咖啡因。这就是为什么母体咖啡因摄入与胎儿发育之间的关系很重要。因此，我们旨在研究母体咖啡因摄入对胎儿和新生儿脑组织中性激素的这种调节作用。妊娠大鼠在怀孕期间和哺乳期饮用含低（0.3 g/L）或高（0.8 g/L）剂量咖啡因的水。在胚胎第 19 天（E19）、出生时（PN0）和出生后第 4 天（PN4），使用放射免疫法测量额叶皮质和下丘脑的睾酮、雌二醇和二氢睾酮水平。低剂量咖啡因的给药增加了 PN4 雄性和雌性大鼠的体重和 PN4 雄性大鼠的肛殖指数。高剂量咖啡因的给药降低了 E19 雄性大鼠的肾上腺重量，并增加了 E19 雌性大鼠额叶皮质和 PN0 雄性大鼠下丘脑的睾酮水平。妊娠期间母体咖啡因的摄入会影响后代额叶皮质和下丘脑中性激素水平。这些大脑中性激素浓度的变化可能会在成年期的某个时候影响行为和神经内分泌功能。
