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阿片促黑皮质素原和垂体限制性转录因子(TPIT)的差异调节,TPIT是正常和腺瘤性人类促肾上腺皮质激素细胞的一种新标志物。

Differential regulation of proopiomelanocortin and pituitary-restricted transcription factor (TPIT), a new marker of normal and adenomatous human corticotrophs.

作者信息

Vallette-Kasic Sophie, Figarella-Branger Dominique, Grino Michel, Pulichino Anne-Marie, Dufour Henry, Grisoli François, Enjalbert Alain, Drouin Jacques, Brue Thierry

机构信息

Unité Mixte de Recherche 6544, Centre National de la Recherche Scientifique, Université de la Méditerranée, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine Nord, 13926 Marseille, France.

出版信息

J Clin Endocrinol Metab. 2003 Jul;88(7):3050-6. doi: 10.1210/jc.2002-021934.

DOI:10.1210/jc.2002-021934
PMID:12843142
Abstract

Since the identification of the pituitary-restricted transcription factor Tpit, a novel T-box factor that is only present in mouse in the two pituitary proopiomelanocortin (POMC)-expressing lineages, no information was available on its pattern of expression in human pituitary. We investigated by immunohistochemistry and in situ hybridization the expression of TPIT in normal human anterior pituitary tissue and in several types of human pituitary adenomas (n = 52). TPIT expression was restricted to the nucleus of normal or adenomatous human corticotroph cells. No specific TPIT immunostaining was detectable in all prolactin (PRL)-, GH-, or gonadotropin-secreting adenomas. In situ hybridization studies demonstrated that TPIT transcripts were coexpressed with POMC mRNA in both secreting and silent corticotroph adenomas, and in normal corticotrophs, whereas TPIT mRNA was not detectable in other types of pituitary adenomas. Unlike POMC, TPIT was not up-regulated by adrenalectomy in rats and did not seem down-regulated in the normal pituitary adjacent to human corticotroph microadenomas. TPIT is the only currently known transcription factor selectively expressed in human normal and adenomatous corticotrophs. In human and experimental models, TPIT and its target gene POMC were thus differentially regulated by glucocorticoids. Moreover, TPIT represents a new marker of POMC-expressing pituitary cells.

摘要

自从鉴定出垂体特异性转录因子Tpit(一种仅在小鼠垂体中表达阿黑皮素原(POMC)的两个细胞谱系中存在的新型T盒因子)以来,关于其在人垂体中的表达模式尚无信息。我们通过免疫组织化学和原位杂交研究了TPIT在正常人类垂体前叶组织和几种类型的人类垂体腺瘤(n = 52)中的表达。TPIT表达局限于正常或腺瘤性人类促肾上腺皮质激素细胞的细胞核。在所有分泌催乳素(PRL)、生长激素(GH)或促性腺激素的腺瘤中均未检测到特异性TPIT免疫染色。原位杂交研究表明,在分泌性和静止性促肾上腺皮质激素腺瘤以及正常促肾上腺皮质激素细胞中,TPIT转录本与POMC mRNA共表达,而在其他类型的垂体腺瘤中未检测到TPIT mRNA。与POMC不同,TPIT在大鼠肾上腺切除术后未上调,在人促肾上腺皮质激素微腺瘤附近的正常垂体中似乎也未下调。TPIT是目前已知的唯一在人正常和腺瘤性促肾上腺皮质激素细胞中选择性表达的转录因子。因此,在人和实验模型中,TPIT及其靶基因POMC受到糖皮质激素的差异调节。此外,TPIT代表了表达POMC的垂体细胞的一种新标记物。

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