Zakaria Marjorie M, Jeong Kyeong-Hoon, Lacza Charlemagne, Kaiser Ursula B
Endocrine-Hypertension Division, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Endocrinol. 2002 Aug;16(8):1840-52. doi: 10.1210/me.2002-0088.
Molecular mechanisms underlying gonadotrope-specific and hormonal regulation of FSHbeta gene expression remain largely unknown. We have studied the role of pituitary homeobox 1 (Ptx1), a transcription factor important for regulation of many pituitary-specific genes, in the regulation of rat FSHbeta (rFSHbeta) gene transcription. We demonstrate that Ptx1 activates the rFSHbeta gene promoter both basally and in synergy with GnRH. The effect of Ptx1 was localized to -140/-50, a region also important for basal activity of the promoter. Two putative Ptx1 binding sites (P1 and P2) homologous to consensus Ptx1 binding elements were identified in this region. We demonstrate specific binding of Ptx1 to the P2 but not to the P1 site. Furthermore, functional studies indicate that the P2 but not the P1 site mediates activation of the promoter by Ptx1. Residual activation of the promoter by Ptx1 was observed independent of the P2 site. However, no additional Ptx1 binding sites were identified in this region, indicating that the residual activation observed is likely independent of direct Ptx1 binding to the promoter. These results identify a functional Ptx1 binding site in the rFSHbeta gene promoter and suggest the presence of an additional activating pathway that is independent of direct binding of Ptx1 to the promoter.
促性腺激素细胞特异性及激素对促卵泡激素β（FSHβ）基因表达调控的分子机制仍不清楚。我们研究了垂体同源框1（Ptx1），一种对许多垂体特异性基因调控很重要的转录因子，在大鼠FSHβ（rFSHβ）基因转录调控中的作用。我们证明Ptx1在基础状态下以及与促性腺激素释放激素（GnRH）协同作用时均可激活rFSHβ基因启动子。Ptx1的作用定位于-140/-50区域，该区域对启动子的基础活性也很重要。在该区域鉴定出两个与Ptx1结合元件共有序列同源的假定Ptx1结合位点（P1和P2）。我们证明Ptx1与P2位点特异性结合，而不与P1位点结合。此外，功能研究表明P2位点而非P1位点介导Ptx1对启动子的激活。观察到Ptx1对启动子的残余激活独立于P2位点。然而，在该区域未鉴定出其他Ptx1结合位点，表明观察到的残余激活可能独立于Ptx1与启动子的直接结合。这些结果确定了rFSHβ基因启动子中的一个功能性Ptx1结合位点，并提示存在一条独立于Ptx1与启动子直接结合的额外激活途径。
