A "hot spot" in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates.
A "hot spot" in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates.
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DOI：
10.1210/jcem.80.2.7852536
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发表时间：
1995-02
期刊：
影响因子：
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通讯作者：
Laurie E. Cohen;F. Wondisford;A. Salvatoni;Mohamad Maghnie;F. Brucker-Davis;B. Weintraub;Sally Radovick
中科院分区：
文献类型：
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作者：
Laurie E. Cohen;F. Wondisford;A. Salvatoni;Mohamad Maghnie;F. Brucker-Davis;B. Weintraub;Sally Radovick
Pit-1是调节哺乳动物发育的POU转录因子家族的成员。PIT-1被认为是垂体前叶中促生长激素细胞和促乳素细胞的主要细胞特异性激活剂。当与DNA结合时，Pit-1激活GH和PRL基因的表达。PIT-1对TRH和cAMP对PRL和TSH-β基因的激素调节也很重要。我们研究了两名GH、PRL和TSH缺乏的无关患者。这两个患者在Pit-1基因的POU同源区域(R271W)有相同的点突变。患者1作为成人进行研究，合并GH、PRL和TSH缺乏。患者2，在婴儿期进行研究，也有GH和PRL缺乏，但甲状腺激素水平低，基础TSH水平可测量，TSH对TRH的延迟反应。因此，目前对导致完全GH、PRL和TSH缺陷的Pit-1基因突变的描述需要扩展到与促甲状腺激素合成能力受损相关的GH和PRL缺陷。
Pit-1 is a member of the POU family of transcription factors regulating mammalian development. Pit-1 is thought to be the major cell-specific activator of both the somatotrophs and lactotrophs in the anterior pituitary. When bound to DNA, Pit-1 activates GH and PRL gene expression. Pit-1 is also important for hormonal regulation of the PRL and TSH-beta genes by TRH and cAMP. We studied two unrelated patients with GH, PRL, and TSH deficiencies. Both patients have the same point mutation in the POU homeodomain of the Pit-1 gene (R271W). Patient 1 was studied as an adult and had combined deficiencies of GH, PRL, and TSH. Patient 2, who was studied in infancy, also had GH and PRL deficiencies, but had low thyroid hormone levels with a measurable basal level of TSH and a delayed response of TSH to TRH. Consequently, the current description of Pit-1 gene mutations leading to complete GH, PRL, and TSH deficiencies needs to be expanded to GH and PRL deficiencies associated with a compromise of the thyrotroph's ability to synthesize TSH.