Department of Anatomy I, Showa University School of Medicine, Tokyo 142-8555, Japan.
Life Sci. 2010 Dec 18;87(23-26):738-42. doi: 10.1016/j.lfs.2010.10.016. Epub 2010 Oct 27.
The early neonatal period is critical for the development of the rodent brain. Neurosteroid levels in the brain decline from the late gestation to the neonatal period. Previous studies indicate effects of neurosteroid treatment during the neonatal period on the development of the dopaminergic system. In this study, we investigated the sex-specific effects of neonatal treatment with the neurosteroid progesterone on monoamine metabolism. Separately, we examined the contribution of pre-pubertal castration on the effect of neonatal treatment of pregnenolone (a neurosteroid precursor).
Progesterone (Experiment 1) or pregnenolone (Experiment 2) treatments in Sprague-Dawley rats were performed from postnatal days 3 through 7. Castration in experiment 2 was performed in male rats at postnatal day 21. We measured the brain tissue contents of dopamine, serotonin (5-HT), and their metabolites in rats at age 10 weeks.
Results showed that neonatal progesterone treatment altered striatal 5-hydroxy-3-indolacetic acid/5-HT ratios in males and females in opposite directions, in addition to dopaminergic effects. The treatment also influenced dopamine and 5-HT metabolism without sex-specificity in the frontal cortex. In addition, there was no significant difference in striatal monoamine metabolism between sham-operated, castrated and castrated pregnenolone-treated group.
The present result indicates a sex-specific influence of progesterone during the early neonatal period on the development of the serotonergic system, depending on brain region in addition to of the dopaminergic system.
啮齿动物大脑的发育在早期新生儿期至关重要。脑内神经甾体水平从妊娠晚期下降到新生儿期。先前的研究表明，新生儿期给予神经甾体治疗对多巴胺能系统的发育有影响。在这项研究中，我们研究了神经甾体孕酮对单胺代谢的新生期治疗的性别特异性影响。此外，我们还研究了青春期前去势对妊娠烯醇酮（神经甾体前体）新生期治疗效果的影响。
在 Sprague-Dawley 大鼠中进行孕酮（实验 1）或孕烯醇酮（实验 2）治疗，从出生后第 3 天至第 7 天。在实验 2 中，雄性大鼠在出生后第 21 天进行去势。我们在 10 周龄时测量大鼠脑组织中多巴胺、血清素（5-HT）及其代谢物的含量。
结果表明，新生期孕酮处理以相反的方向改变了雄性和雌性大鼠纹状体 5-羟吲哚乙酸/5-HT 比值，除了多巴胺能作用外。该处理还影响了前额皮质中没有性别特异性的多巴胺和 5-HT 代谢。此外，假手术、去势和去势妊娠烯醇酮处理组之间纹状体单胺代谢无显著差异。
本研究结果表明，孕酮在早期新生儿期对发育中的 5-HT 系统的影响具有性别特异性，除了多巴胺能系统外，还取决于大脑区域。
