Forkhead Box O1 is present in quiescent pituitary cells during development and is increased in the absence of p27 Kip1.
Forkhead Box O1 is present in quiescent pituitary cells during development and is increased in the absence of p27 Kip1.
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DOI：
10.1371/journal.pone.0052136
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ellsworth BS
中科院分区：
文献类型：
--
作者：
Majumdar S;Farris CL;Kabat BE;Jung DO;Ellsworth BS
据报道，先天性垂体激素缺乏症约有4000例活产婴儿中有1例，然而，研究报告一些广泛研究的转录因子突变仅占人类先天性激素缺乏症的一小部分。包括性腺、肾上腺和甲状腺在内的几个腺体的发育和功能都需要垂体前叶激素。为了确定导致人类先天性激素缺乏的其他因素，我们正在研究叉头转录因子fox01，它与包括卵巢、睾丸和大脑在内的几个器官的发育有关。我们发现fox01在胚胎发育期间存在于未分裂的垂体细胞的细胞核中，与限制增殖和/或促进分化的作用一致。fox01存在于18.5岁的分化细胞亚群中，在成人中表达水平最高的是生长斜体细胞。我们在e14.5的p27kip1阳性细胞中检测到FOXO1。在p27Kip1缺失的情况下，含有FOXO1的垂体细胞数量在e14.5时显著增加，这表明FOXO1和p27Kip1之间的相互作用受到反馈回路的调节。
Congenital pituitary hormone deficiencies have been reported in approximately one in 4,000 live births, however studies reporting mutations in some widely studied transcription factors account for only a fraction of congenital hormone deficiencies in humans. Anterior pituitary hormones are required for development and function of several glands including gonads, adrenals, and thyroid. In order to identify additional factors that contribute to human congenital hormone deficiencies, we are investigating the forkhead transcription factor, FOXO1, which has been implicated in development of several organs including ovary, testis, and brain. We find that FOXO1 is present in the nuclei of non-dividing pituitary cells during embryonic development, consistent with a role in limiting proliferation and/or promoting differentiation. FOXO1 is present in a subset of differentiated cells at e18.5 and in adult with highest level of expression in somatotrope cells. We detected FOXO1 in p27Kip1-positive cells at e14.5. In the absence of p27Kip1 the number of pituitary cells containing FOXO1 is significantly increased at e14.5 suggesting that a feedback loop regulates the interplay between FOXO1 and p27Kip1.
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