Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, Kraków, Poland.
Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, Kraków, Poland.
Pharmacol Rep. 2019 Apr;71(2):347-350. doi: 10.1016/j.pharep.2018.11.003. Epub 2018 Nov 28.
Corticosteroid-binding globulin (CBG), albumin and 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes play crucial roles in the bioavailability of glucocorticoids. Downstream of the adrenal glands, these proteins affect glucocorticoid levels in target tissues. Early-life stress (ELS) is known to program glucocorticoid action at many levels. The effects of ELS on the concentrations and synthesis of CBG and albumin and on the expression of 11β-HSD remain unclear.
The maternal separation (MS) procedure in rats on postnatal days 1-14 was used as a model of ELS. On postnatal day 35 (adolescence), the serum corticosterone, CBG and albumin concentrations of male rats were measured by ELISA, while the mRNA and protein levels of CBG, albumin and 11β-HSD1 in the liver and brain were examined by RT-qPCR and Western blot, respectively.
Under basal conditions, MS rats displayed lower levels of serum CBG and albumin. However, MS did not affect CBG or albumin synthesis in the liver, suggesting that the half-life and/or secretion of these proteins were influenced by MS. Additionally, MS rats showed increased protein expression of 11β-HSD1, specifically in the medial prefrontal cortex.
These results indicate that ELS may potentially program glucocorticoid action through its effects on glucocorticoid bioavailability in tissues.
皮质甾醇结合球蛋白（CBG）、白蛋白和 11β-羟甾类脱氢酶（11β-HSD）在糖皮质激素的生物利用度中起着至关重要的作用。在肾上腺下游，这些蛋白质影响糖皮质激素在靶组织中的水平。众所周知，早期生活应激（ELS）会在多个层面上编程糖皮质激素的作用。ELS 对 CBG 和白蛋白的浓度和合成以及 11β-HSD 的表达的影响尚不清楚。
在产后第 1-14 天对大鼠进行母体分离（MS）程序，作为 ELS 的模型。在第 35 天（青春期），通过 ELISA 测量雄性大鼠的血清皮质酮、CBG 和白蛋白浓度，同时通过 RT-qPCR 和 Western blot 分别检测肝脏和大脑中 CBG、白蛋白和 11β-HSD1 的 mRNA 和蛋白水平。
在基础条件下，MS 大鼠的血清 CBG 和白蛋白水平较低。然而，MS 并未影响肝脏中 CBG 或白蛋白的合成，这表明这些蛋白质的半衰期和/或分泌受到 MS 的影响。此外，MS 大鼠的 11β-HSD1 蛋白表达增加，特别是在中前额皮质。
这些结果表明，ELS 可能通过其对组织中糖皮质激素生物利用度的影响来编程糖皮质激素作用。
