Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis.
Roles of progranulin in sexual differentiation of the developing brain and adult neurogenesis.
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前植物在发育中的大脑和成人神经发生的性分化中的作用。
DOI：
10.1262/jrd.20249
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Nishihara M
中科院分区：
文献类型：
--
作者：
Suzuki M;Lee HC;Kayasuga Y;Chiba S;Nedachi T;Matsuwaki T;Yamanouchi K;Nishihara M
颗粒体蛋白前体 (PGRN) 是多种细胞释放的生长调节因子。最近发现 PGRN 在正常大脑和神经退行性疾病中的多功能作用，该分子引起了神经科学界的关注。我们重点关注 PGRN 作为性类固醇响应基因在发育中和成年啮齿动物大脑中的新作用。虽然发育中的大脑默认是女性化的，但激素暴露，包括雄激素和雌激素，会在关键时期诱导肌肉化。我们已经证明 PGRN 是一种性类固醇相关基因，可能参与围产期大鼠大脑的雄性化。我们还发现，成年大鼠海马中 PGRN 基因表达受到雌激素的上调，表明 PGRN 可能介导雌激素在神经发生活跃区域的促有丝分裂作用。由于最近有报道称 PGRN 基因突变导致人类额颞叶变性，因此 PGRN 似乎也参与调节神经变性。总之，PGRN 基因表达是由雌激素在发育中和成人大脑中诱导的，并且它可能在发育中大脑的功能性男性化组织和成人大脑功能的维持中发挥多功能作用。
Progranulin (PGRN) is a growth modulating factor released by a variety of cells. This molecule has gained the attention of the neuroscience community with recent discoveries of multifunctional roles of PGRN in normal brain and neurodegenerative disorders. We focus on novel roles of PGRN as a sex steroid-responsible gene in the developing and adult rodent brain. While the developing brain is feminine by default, hormone exposure, including androgen and estrogen, induces musculinization during the critical period. We have shown that PGRN is a sex steroid-responsible gene that may be involved in masculinization of the perinatal rat brain. We also found that in adult rats PGRN gene expression was up-regulated by estrogen in the hippocampus, suggesting that PGRN may mediate the mitogenic effects of estrogen in the active area of neurogenesis. Since it has been recently reported that mutations in PGRN gene are responsible for a type of frontotemporal lobar degeneration in humans, PGRN appears to be also involved in modulating neurodegeneration. Together, PGRN gene expression is induced by estrogen in both developing and adult brains, and it may play multifunctional roles in the organization of functional masculinization in the developing brain and the maintenance of adult brain function.
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