Mizokami Yoshihito, Egashira Noboru, Takekoshi Susumu, Itoh Johbu, Itoh Yoshiko, Osamura Robert Yoshiyuki, Matsumae Mitsunori
Department of Neurosurgery, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.
Endocr Pathol. 2008 Spring;19(1):54-61. doi: 10.1007/s12022-008-9021-7.
Transcription factors play specific roles in the development and differentiation of normal pituitary tissues and pituitary adenoma. The transcription factor, muscle segment homeobox 1 (MSX1), which belongs to the homeobox gene family, binds the promoter region of the glycoprotein hormone alpha-subunit (SU) in TSH-producing cells in the mouse pituitary and regulates alpha-SU expression. The present study investigated MSX1 expression in the normal human pituitary. In addition, 50 pituitary adenomas were examined using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) to clarify the role of MSX1 in the development and functional differentiation of pituitary adenoma cells. In the normal pituitary, MSX1 was predominantly expressed in the cytoplasm of GH-producing cells. Furthermore, MSX1 immunoreactivity was observed in the cytoplasm of some alpha-SU-producing cells. It is interesting to note that, in the pituitary adenoma, MSX1 was expressed in the nucleus of GH- and TSH-producing adenomas. RT-PCR using RNA extracted and purified from formalin-fixed paraffin-embedded pituitary adenoma specimens revealed MSX1 mRNA expressed in GH- and TSH-producing adenomas. Immunoelectron microscopy demonstrated MSX1 localized at intranuclear heterochromatin and euchromatin, which suggests transcriptional activity. These results suggest that MSX1 plays a specific role in human pituitary adenoma.
转录因子在正常垂体组织和垂体腺瘤的发育及分化过程中发挥着特定作用。属于同源框基因家族的转录因子肌肉节段同源框1(MSX1),可与小鼠垂体中促甲状腺激素分泌细胞内糖蛋白激素α亚基(SU)的启动子区域结合,并调节α-SU的表达。本研究调查了MSX1在正常人体垂体中的表达情况。此外,运用免疫组织化学和逆转录聚合酶链反应(RT-PCR)对50例垂体腺瘤进行检测,以阐明MSX1在垂体腺瘤细胞发育及功能分化中的作用。在正常垂体中,MSX1主要在生长激素分泌细胞的细胞质中表达。此外,在一些促甲状腺激素释放激素分泌细胞的细胞质中也观察到了MSX1免疫反应性。值得注意的是,在垂体腺瘤中,MSX1在生长激素分泌型和促甲状腺激素分泌型腺瘤的细胞核中表达。使用从福尔马林固定石蜡包埋的垂体腺瘤标本中提取并纯化的RNA进行RT-PCR,结果显示生长激素分泌型和促甲状腺激素分泌型腺瘤中均表达MSX1 mRNA。免疫电子显微镜显示MSX1定位于核内异染色质和常染色质,这表明其具有转录活性。这些结果表明MSX1在人类垂体腺瘤中发挥着特定作用。