Steinfelder H J, Wondisford F E
Institute of Pharmacology and Toxicology, University of Göttingen, Germany.
Exp Clin Endocrinol Diabetes. 1997;105(4):196-203. doi: 10.1055/s-0029-1211751.
Synthesis of pituitary hormones was shown to be efficiently regulated at the transcriptional level. The specialized function of the five cell types in the anterior pituitary is controlled by ubiquitous as well as cell-specific transcription factors. Pit-1 is such a cell-specific regulator found only in lacto-, somato- and thyrotropes which could be shown to be essential for basal expression of growth hormone (GH) and prolactin (Prl) genes and the regulated expression of Prl and thyrotropin (TSH) beta-subunit genes. Identification of distinct binding sites for transcription factors and some of the mechanisms of transcriptional control shed light on the complex regulation of pituitary hormone gene expression which is exemplified for the TSH beta gene. The control of basal as well as positively and negatively regulated expression of some pituitary hormone genes becomes fairly well understood by the investigation of the role of Pit-1. Identification of different mutations in the human pit-1 gene supported the role of this protein for combined pituitary hormone deficiency (CPHD) characterized by the deficiency of GH, prolactin and TSH.
垂体激素的合成在转录水平上被证明受到有效调控。垂体前叶中五种细胞类型的特殊功能由普遍存在的以及细胞特异性转录因子控制。Pit-1就是这样一种仅在催乳素细胞、生长激素细胞和促甲状腺激素细胞中发现的细胞特异性调节因子,已证明它对于生长激素(GH)和催乳素(Prl)基因的基础表达以及Prl和促甲状腺激素(TSH)β亚基基因的调控表达至关重要。转录因子不同结合位点的鉴定以及一些转录控制机制揭示了垂体激素基因表达的复杂调控,TSHβ基因就是一个例证。通过对Pit-1作用的研究,对一些垂体激素基因的基础表达以及正负调控表达的控制有了相当深入的了解。人类pit-1基因中不同突变的鉴定支持了这种蛋白质在以GH、催乳素和TSH缺乏为特征的联合垂体激素缺乏症(CPHD)中的作用。