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垂体特异性转录因子信使核糖核酸在人垂体腺瘤组织和非肿瘤性垂体组织中的表达

Pituitary specific transcription factor messenger ribonucleic expression in adenomatous and nontumorous human pituitary tissues.

作者信息

Lloyd R V, Jin L, Chandler W F, Horvath E, Stefaneanu L, Kovacs K

机构信息

Department of Pathology and Surgery (Neurosurgery Section) University of Michigan, Ann Arbor.

出版信息

Lab Invest. 1993 Nov;69(5):570-5.

PMID:8246449
Abstract

BACKGROUND

The pituitary-specific transcription factor, Pit-1/GHF-1 (Pit-1) is a member of the POU family of homeobox genes. This transacting factor has a role in the development and expression of selected anterior pituitary cells including prolactin, growth hormone (GH), and thyrotropin, cell types in rodent pituitary. The expression of Pit-1 mRNA in human pituitaries has not been previously analyzed and the role of specific secretagogues in the regulation of Pit-1 transcripts in human pituitary adenomas has not been examined. Analysis of Pit-1 expression in normal and neoplastic human pituitaries may provide insight into the specificity of this transcription factor for pituitary cell types and the role of Pit-1 in human pituitary function.

EXPERIMENTAL DESIGN

In situ and Northern hybridization analyses were used to study the expression of Pit-1 mRNA in surgically removed human pituitary adenomas and nontumorous pituitaries obtained within 6 hours postmortem. A cultured GH surgically removed adenoma was used to analyze the regulation of GH and Pit-1 in vitro.

RESULTS

In situ hybridization localized Pit-1 mRNA in all pituitary adenomas, although the mRNA levels in GH and prolactin adenomas were significantly higher than those in ACTH, null cell and gonadotroph tumors. Northern hybridization analysis revealed a 2.4 and a 1.2 kb mRNA transcript for Pit-1. Although GH mRNA transcript was markedly changed by dexamethasone and phorbol 12-myristate 13-acetate in vitro, Pit-1 mRNA transcripts were not changed significantly by these secretagogues.

CONCLUSIONS

Pit-1 mRNA transcripts are expressed mainly in prolactin and GH pituitary adenomas, but are also found in other adenomas and in the nontumorous adult human pituitary. Pit-1 mRNA transcript levels are not readily modulated in cultured GH adenoma cells by various secretagogues in vitro compared with the marked modulation of GH mRNA transcripts by these same secretagogues.

摘要

背景

垂体特异性转录因子Pit-1/GHF-1(Pit-1)是同源框基因POU家族的成员。这种反式作用因子在包括催乳素、生长激素(GH)和促甲状腺激素在内的特定垂体前叶细胞的发育和表达中发挥作用,这些细胞类型存在于啮齿动物的垂体中。此前尚未对人垂体中Pit-1 mRNA的表达进行分析,也未研究特定促分泌素在人垂体腺瘤中对Pit-1转录本的调节作用。分析正常和肿瘤性人垂体中Pit-1的表达可能有助于深入了解该转录因子对垂体细胞类型的特异性以及Pit-1在人垂体功能中的作用。

实验设计

采用原位杂交和Northern杂交分析方法,研究手术切除的人垂体腺瘤以及死后6小时内获取的非肿瘤性垂体中Pit-1 mRNA的表达。使用手术切除的培养GH腺瘤分析体外GH和Pit-1的调节情况。

结果

原位杂交将Pit-1 mRNA定位在所有垂体腺瘤中,尽管GH和催乳素腺瘤中的mRNA水平显著高于促肾上腺皮质激素(ACTH)、无功能细胞和促性腺激素肿瘤中的水平。Northern杂交分析显示Pit-1有2.4 kb和1.2 kb的mRNA转录本。虽然体外地塞米松和佛波酯12-肉豆蔻酸酯13-乙酸酯可显著改变GH mRNA转录本,但这些促分泌素对Pit-1 mRNA转录本的影响不明显。

结论

Pit-1 mRNA转录本主要在催乳素和GH垂体腺瘤中表达,但在其他腺瘤和非肿瘤性成人垂体中也可检测到。与这些促分泌素对GH mRNA转录本的显著调节相比,体外各种促分泌素对培养的GH腺瘤细胞中Pit-1 mRNA转录本水平的调节作用不明显。

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