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青春期和成年雄性大鼠海马中糖皮质激素受体易位及相关基因表达

Glucocorticoid receptor translocation and expression of relevant genes in the hippocampus of adolescent and adult male rats.

作者信息

Green Matthew R, Nottrodt Rachel E, Simone Jonathan J, McCormick Cheryl M

机构信息

Department of Psychology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S3A1, Canada.

Department of Biology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S3A1, Canada.

出版信息

Psychoneuroendocrinology. 2016 Nov;73:32-41. doi: 10.1016/j.psyneuen.2016.07.210. Epub 2016 Jul 16.


DOI:10.1016/j.psyneuen.2016.07.210
PMID:27448526
Abstract

We investigated whether pre-pubertal (postnatal day [P] 35) and post-pubertal adolescent (P45) and adult (P75) male rats differed in stressor-induced hormonal responses and in glucocorticoid receptor (GR) translocation because it has been proposed that negative feedback is maturing in adolescence and may be a basis for the prolonged activation of the HPA axis in adolescents compared with adults. The three age groups did not differ at baseline in plasma corticosterone or progesterone concentrations, and P35 had lower concentrations of testosterone than did both P45 and P75 rats, which did not differ. After 30min of restraint stress, plasma concentrations of corticosterone and progesterone increased to a greater extent in the adolescents than in the adults. Whereas restraint stress increased concentrations of testosterone in adult males, concentrations decreased in adolescents. In all three age groups, restraint stress reduced GR expression in the cytosol and increased expression in the nucleus within the hippocampus, and the increase in nuclear GR was greater in pre-pubertal adolescents compared with adults. In a separate set of rats we investigated age differences in hippocampal mRNA expression of corticosteroid receptors (MR and GR) and of chaperones (FKBP5, FKBP4, BAG-1), which are known to modulate their activity, at baseline and after restraint stress. Restraint stress decreased the expression of GR and increased the expression of FKBP5 mRNA, and age was not a significant factor. Higher expression of FKBP4 mRNA was found at P35 than at P75. Most research of HPA function in adolescent rats has involved pre-pubertal rats; the present findings indicate that despite their increase in gonadal function, responses to stressors in P45 rats are more like those of pre-pubertal than adult rats. The greater stressor-induced GR translocation in pre-pubertal adolescents parallels their greater release of corticosterone in response to stressors, which may contribute to the enhanced sensitivity of adolescent rats to the effects of chronic stress exposures compared with adults.

摘要

我们研究了青春期前(出生后第[P]35天)、青春期后青少年期(P45)和成年期(P75)雄性大鼠在应激源诱导的激素反应以及糖皮质激素受体(GR)易位方面是否存在差异,因为有观点认为负反馈在青春期正在成熟,这可能是青少年与成年人相比HPA轴长期激活的一个基础。三个年龄组在基线时血浆皮质酮或孕酮浓度并无差异,且P35大鼠的睾酮浓度低于P45和P75大鼠,而后两者无差异。在约束应激30分钟后,青少年大鼠血浆皮质酮和孕酮浓度的升高幅度大于成年大鼠。虽然约束应激会使成年雄性大鼠的睾酮浓度升高,但青少年大鼠的睾酮浓度却降低。在所有三个年龄组中,约束应激均降低了海马体细胞质中GR的表达,并增加了细胞核中的表达,且青春期前青少年细胞核GR的增加幅度大于成年大鼠。在另一组大鼠中,我们研究了在基线和约束应激后,海马体中糖皮质激素受体(MR和GR)以及伴侣蛋白(FKBP5、FKBP4、BAG-1)的mRNA表达的年龄差异,已知这些伴侣蛋白会调节它们的活性。约束应激降低了GR的表达并增加了FKBP5 mRNA的表达,年龄并非显著因素。发现P35时FKBP4 mRNA的表达高于P75时。大多数关于青少年大鼠HPA功能的研究都涉及青春期前大鼠;目前的研究结果表明,尽管P45大鼠的性腺功能有所增强,但其对应激源的反应更类似于青春期前而非成年大鼠。青春期前青少年中更大的应激源诱导的GR易位与其对应激源更大的皮质酮释放相平行,这可能导致青少年大鼠与成年大鼠相比对慢性应激暴露的影响更为敏感。

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