Tagawa Noriko, Sugimoto Yumi, Yamada Jun, Kobayashi Yoshiharu
Department of Medical Biochemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Kobe 658-8558, Japan.
Steroids. 2006 Sep;71(9):776-84. doi: 10.1016/j.steroids.2006.05.008. Epub 2006 Jun 23.
Neurosteroids, pregnenolone (Preg), dehydroepiandrosterone (DHEA) and their sulfates (PregS and DHEAS) are reported to exert their modulatory effects of neuronal excitability and synaptic plasticity via amino acid receptors, which affect and regulate the learning and memory process, mood, and depression. Although the brain levels of these steroids have been reported in rodents, the strain differences of the levels of these steroids have not been demonstrated. We examined the concentrations of Preg, 17-OH-Preg, DHEA, androstenediol (ADIOL) and their sulfates in whole brains from DBA/2, C57BL/6, BALB/c, ddY and ICR mice, the genetic backgrounds of which are different. No differences in the brain levels of Preg and DHEA were found among the strains. In contrast, PregS levels in DBA/2 were significantly lower than in the others, while DHEAS concentrations in DBA/2 were significantly higher than those in other strains. Strain differences were found in 17-OH-Preg, ADIOL and 17-OH-PregS but not in ADIOLS levels. The ranges of Preg and PregS levels were the highest among the steroids studied. Further, we measured serum these steroid levels. Although strain differences were also found in serum steroids, correlation study between brain and serum levels revealed that brain neurosteroids studied may not come from peripheral circulation. In conclusion, this is the first report of demonstrating mammalian brain levels of 17-OH-Preg, ADIOL, 17-OH-PregS and ADIOLS and the strain differences in neurosteroid levels in mice brains. The differences in levels may involve the strain differences in their behavior, e.g. aggression, adaptation to stress or learning, in mice.
据报道，神经甾体、孕烯醇酮（Preg）、脱氢表雄酮（DHEA）及其硫酸盐（PregS和DHEAS）通过氨基酸受体发挥对神经元兴奋性和突触可塑性的调节作用，而这些氨基酸受体影响和调节学习与记忆过程、情绪及抑郁状态。尽管已报道了啮齿动物大脑中这些甾体的水平，但尚未证实这些甾体水平存在品系差异。我们检测了基因背景不同的DBA/2、C57BL/6、BALB/c、ddY和ICR小鼠全脑中Preg、17-羟基孕烯醇酮（17-OH-Preg）、DHEA、雄烯二醇（ADIOL）及其硫酸盐的浓度。在各品系中未发现Preg和DHEA的脑内水平存在差异。相反，DBA/2小鼠的PregS水平显著低于其他品系，而DBA/2小鼠的DHEAS浓度显著高于其他品系。在17-OH-Preg、ADIOL和17-羟基孕烯醇酮硫酸盐（17-OH-PregS）中发现了品系差异，但在雄烯二醇硫酸盐（ADIOLS）水平上未发现差异。在所研究的甾体中，Preg和PregS水平的范围最高。此外，我们检测了血清中这些甾体的水平。尽管在血清甾体中也发现了品系差异，但脑内和血清水平之间的相关性研究表明，所研究的脑内神经甾体可能并非来自外周循环。总之，这是首次报道证明哺乳动物脑内17-OH-Preg、ADIOL、17-OH-PregS和ADIOLS的水平以及小鼠脑内神经甾体水平的品系差异。这些水平差异可能与小鼠行为的品系差异有关，例如攻击性、对压力的适应性或学习能力。
