Previous studies have indicated that sex hormones such as prolactin, estradiol and testosterone may play a role in the modulation of adult hippocampal neurogenesis (AHN) in rodents and non-human primates, but so far there has been no investigation of their impact on human hippocampal neurogenesis. Here, we quantify the expression levels of the relevant receptors in human post-mortem hippocampal tissue and a human hippocampal progenitor cell (HPC) line. Secondly, we investigate how these hormones modulate hippocampal neurogenesis using a human in vitro cellular model. Human female HPCs were cultured with biologically relevant concentrations of either prolactin, estradiol or testosterone. Bromodeoxyuridine (BrdU) incorporation, immunocytochemistry (ICC) and high-throughput analyses were used to quantify markers determining cell fate after HPCs were either maintained in a proliferative state or allowed to differentiate in the presence of these hormones. In proliferating cells, estrogen and testosterone increased cell density but had no clear effect on markers of proliferation or cell death to account for this. In differentiating cells, a 3-day treatment of prolactin elicited a transient effect, whereby it increased the proportion of microtubule-associated protein 2 (MAP2)-positive and Doublecortin (DCX)-positive cells, but this effect was not apparent after 7-days. At this timepoint we instead observe a decrease in proliferation. Overall, our study demonstrates relatively minor, and possibly short-term effects of sex hormones on hippocampal neurogenesis in human cells. Further work will be needed to understand if our results differ to previous animal research due to species-specific differences, or whether it relates to limitations of our in vitro model.

中文翻译：

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催乳素，雌二醇和睾丸激素在体外模型中差异影响人海马神经发生。

先前的研究表明，性激素如催乳激素，雌二醇和睾丸激素可能在啮齿动物和非人类灵长类动物的成年海马神经发生（AHN）的调节中起作用，但是到目前为止，尚未研究它们对人海马的影响神经发生。在这里，我们量化人类验尸海马组织和人类海马祖细胞（HPC）系中相关受体的表达水平。其次，我们使用人类体外细胞模型研究这些激素如何调节海马神经发生。用生物学相关浓度的催乳素，雌二醇或睾丸激素培养人类女性HPC。结合溴脱氧尿苷（BrdU）免疫细胞化学（ICC）和高通量分析被用于量化HPC保持增殖状态或在这些激素存在下分化后确定细胞命运的标志物。在增殖的细胞中，雌激素和睾丸激素可增加细胞密度，但对增殖或细胞死亡的标志物没有明显的影响。在分化细胞中，催乳素进行3天的治疗会引起短暂的作用，从而增加了微管相关蛋白2（MAP2）阳性和双皮质素（DCX）阳性细胞的比例，但这种作用在7-天。在这个时间点上，我们观察到增殖减少。总体而言，我们的研究表明，性激素对人细胞海马神经发生的影响相对较小，甚至可能是短期的。