Miyai Shunsuke, Yoshimura Shinichi, Iwasaki Yasumasa, Takekoshi Susumu, Lloyd Ricardo V, Osamura Robert Yoshiyuki
Department of Pathology, Tokai University School of Medicine, Bohseidai Isehara Campus, Kanagawa 259-1193, Japan.
Cell Tissue Res. 2005 Nov;322(2):269-77. doi: 10.1007/s00441-005-0033-z. Epub 2005 Nov 3.
The functional development of pituitary cells depends on the expression of a combination of transcription factors and co-factors. Pituitary-specific transcription factor-1 (Pit-1) is required for the expression of growth hormone (GH), prolactin (PRL), and the thyroid-stimulating hormone beta subunit (TSH beta) and acts synergistically with the estrogen receptor (ER) and GATA-binding protein 2 (GATA-2) to induce PRL and TSH beta expression, respectively. The glycoprotein hormone alpha subunit (alpha SU) is the first hormone to be expressed during pituitary development. In addition to being expressed in follicle-stimulating hormone, luteinizing hormone (LH), and TSH cells, alpha SU is reported to co-localize with GH in pituitary cells. These findings have led to the suggestion that the expression of Pit-1 in cells of the alpha SU-based gonadotropin cell lineage might also lead to the expression of GH. In this study, we transfected HP 75 cells (derived from a human non-functioning pituitary adenoma that expressed alpha SU and LH beta) with Pit-1 by using an adenovirus FLAG-Pit-1 construct. Most of the transfected cells expressed GH mRNA, with fewer cells expressing PRL and TSH beta mRNA. The HP 75 cells expressed the genes for ER and GATA-2, thus allowing their expression of GH, PRL, and TSH beta mRNA in response to Pit-1. These results support the hypothesis that GH can be induced in cells that possess an active alpha SU gene and shed light on the basic molecular mechanism that drives the development of GH, PRL, and TSH beta expression in the alpha SU-based gonadotroph lineage.
垂体细胞的功能发育取决于多种转录因子和辅助因子的组合表达。垂体特异性转录因子-1（Pit-1）是生长激素（GH）、催乳素（PRL）和促甲状腺激素β亚基（TSHβ）表达所必需的，并且分别与雌激素受体（ER）和GATA结合蛋白2（GATA-2）协同作用以诱导PRL和TSHβ的表达。糖蛋白激素α亚基（αSU）是垂体发育过程中最早表达的激素。除了在促卵泡激素、黄体生成素（LH）和TSH细胞中表达外，据报道αSU在垂体细胞中与GH共定位。这些发现提示，在基于αSU的促性腺激素细胞系细胞中Pit-1的表达也可能导致GH的表达。在本研究中，我们使用腺病毒FLAG-Pit-1构建体将Pit-1转染至HP 75细胞（源自表达αSU和LHβ的人无功能垂体腺瘤）。大多数转染细胞表达GH mRNA，较少细胞表达PRL和TSHβ mRNA。HP 75细胞表达ER和GATA-2的基因，因此使其能够响应Pit-1表达GH、PRL和TSHβ mRNA。这些结果支持了在具有活性αSU基因的细胞中可诱导GH表达的假说，并揭示了驱动基于αSU的促性腺激素细胞系中GH、PRL和TSHβ表达发育的基本分子机制。
