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催乳素对成年小鼠脉络丛胰岛素样生长因子 2 基因表达的调节作用。

Prolactin regulation of insulin-like growth factor 2 gene expression in the adult mouse choroid plexus.

机构信息

Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Department of Anatomy, School of Medical Sciences, University of Otago, Dunedin, New Zealand.

出版信息

FASEB J. 2019 May;33(5):6115-6128. doi: 10.1096/fj.201802262R. Epub 2019 Feb 8.

Abstract

There is clear evidence for carrier-mediated transport of prolactin into the brain, and it has been widely assumed that prolactin receptors (PRLRs) in the choroid plexus (ChP) might mediate this transport. Using PRLR knockout mice, we recently showed that PRLRs in ChP are not required for prolactin transport into the brain. Hence, the function of PRLR in the ChP remains unknown. PRLR expression is increased in the ChP during lactation, suggesting a possible role in adaptive function of prolactin at this time. To gain insight into prolactin function in the ChP, we have utilized RNA sequencing and NanoString techniques to characterize transcriptional changes in response to differing levels of prolactin at diestrus, during pregnancy, and in lactation. We have observed opposing transcriptional effects of prolactin on the ChP in different physiologic states, being primarily inhibitory during diestrus but stimulatory in lactation. Insulin-like growth factor 2 (), a highly expressing transcript found in the ChP, showed a 6-fold increase at lactation that returned to baseline on suppression of prolactin levels. These results indicate that may be an important downstream mediator of prolactin-induced signaling in the ChP.-Phillipps, H. R., Rand, C. J., Brown, R. S. E., Kokay, I. C., Stanton, J.-A., Grattan, D. R. Prolactin regulation of insulin-like growth factor 2 gene expression in the adult mouse choroid plexus.

摘要

有明确的证据表明催乳素是通过载体介导进入大脑的,人们普遍认为脉络丛(ChP)中的催乳素受体(PRLR)可能介导这种转运。我们最近使用 PRLR 敲除小鼠表明,ChP 中的 PRLR 对于催乳素向大脑的转运不是必需的。因此,PRLR 在 ChP 中的功能仍然未知。在哺乳期,ChP 中的 PRLR 表达增加,表明其在此时催乳素的适应性功能中可能发挥作用。为了深入了解催乳素在 ChP 中的功能,我们利用 RNA 测序和 NanoString 技术来描述催乳素在动情期、怀孕期间和哺乳期不同水平下对 ChP 转录变化的影响。我们观察到催乳素在不同生理状态下对 ChP 产生相反的转录效应,在动情期主要是抑制作用,但在哺乳期是刺激作用。胰岛素样生长因子 2()是 ChP 中高表达的转录本,在哺乳期时增加了 6 倍,在催乳素水平受到抑制时恢复到基线。这些结果表明,在 ChP 中,可能是催乳素诱导信号的重要下游介质。

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