Asa S L, Puy L A, Lew A M, Sundmark V C, Elsholtz H P
Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 1993 Nov;77(5):1275-80. doi: 10.1210/jcem.77.5.8077321.
Pit-1 is a transcription factor that has been shown to be critical for pituitary-specific activation of the GH and PRL genes. In rodents and humans, differentiation and/or maintenance of somatotroph, lactotroph, and thyrotroph phenotypes are dependent on expression of a functional pit-1 gene. In rodents, Pit-1 protein is detectable in only these three cell types; however, pit-1 mRNA transcripts appear to be present at comparable levels in all adenohypophysial cell types, suggesting that translational controls may dictate the pattern of Pit-1 expression. We examined the distribution of pit-1 transcripts in the human pituitary and pituitary adenomas. All tumors were characterized by immunocytochemistry, electron microscopy, and tissue culture for accurate classification. Northern blot analysis demonstrated abundant levels of pit-1 mRNA in somatotroph, mammosomatotroph, and lactotroph adenomas. Two clinically silent adenomas that expressed TSH as well as gonadotropins contained detectable levels of pit-1 mRNA. No pit-1 expression was otherwise detected in corticotroph, gonadotroph, null cell, or oncocytic adenomas. In situ hybridization localized pit-1 mRNA transcripts in adenomas that contained GH, PRL, or TSH, but not in adenomas composed of other cell types. Pit-1 mRNA was also localized to selected subpopulations of the human nontumorous adenohypophysis that contained immunoreactivity for GH, PRL, and/or TSH. Pit-1 protein immunoreactivity was detected in the nuclei of adenomas that expressed pit-1 mRNA, but not in those that were negative for pit-1 mRNA; it was also localized only in cells containing GH, PRL, or TSH beta in the nontumorous adenohypophysis. These data demonstrate selective expression of the human pit-1 gene in adenohypophysial cell types responsible for GH, PRL, and/or TSH synthesis and are consistent with a predominantly pretranslational regulatory mechanism for Pit-1 expression in the human.
Pit-1是一种转录因子，已被证明对生长激素（GH）和催乳素（PRL）基因的垂体特异性激活至关重要。在啮齿动物和人类中，生长激素细胞、催乳素细胞和促甲状腺激素细胞表型的分化和/或维持依赖于功能性pit-1基因的表达。在啮齿动物中，仅在这三种细胞类型中可检测到Pit-1蛋白；然而，pit-1 mRNA转录本似乎在所有腺垂体细胞类型中以相当的水平存在，这表明翻译控制可能决定Pit-1的表达模式。我们研究了pit-1转录本在人垂体和垂体腺瘤中的分布。所有肿瘤均通过免疫细胞化学、电子显微镜和组织培养进行特征性分析以进行准确分类。Northern印迹分析表明，生长激素细胞腺瘤、乳腺生长激素细胞腺瘤和催乳素细胞腺瘤中pit-1 mRNA水平丰富。两个表达促甲状腺激素以及促性腺激素的临床无功能性腺瘤含有可检测水平的pit-1 mRNA。在促肾上腺皮质激素细胞腺瘤、促性腺激素细胞腺瘤、无功能细胞腺瘤或嗜酸细胞瘤中未检测到其他pit-1表达。原位杂交将pit-1 mRNA转录本定位在含有GH、PRL或TSH的腺瘤中，但在由其他细胞类型组成的腺瘤中未定位到。Pit-1 mRNA也定位到人类非肿瘤性腺垂体中对GH、PRL和/或TSH具有免疫反应性的选定亚群。在表达pit-1 mRNA的腺瘤细胞核中检测到Pit-1蛋白免疫反应性，但在pit-1 mRNA阴性的腺瘤中未检测到；它也仅定位在非肿瘤性腺垂体中含有GH、PRL或TSHβ的细胞中。这些数据证明了人类pit-1基因在负责GH、PRL和/或TSH合成的腺垂体细胞类型中的选择性表达，并且与人类中Pit-1表达主要的翻译前调节机制一致。
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