Activation of the glycoprotein hormone alpha-subunit gene promoter in thyrotropes

Pituitary expression of the glycoprotein hormone alpha-subunit gene localiz es to thyrotropes and gonadotropes. Factors that activate the alpha-subunit promoter exclusively in thyrotropes have not been described. In the curren t studies, alpha-subunit promoter activity was compared in alpha TSH thyrot ropic and alpha T3 gonadotropic cells. Deletional analysis revealed a more important contribution of the - 453/- 381 region in thyrotropic cells and t he - 341/ - 297 region in gonadotropic cells, while other deletions had sim ilar effects. Mutational analysis revealed some regions that were functiona lly similar, while others were active only in thyrotropic cells, such as th e regions - 434/ - 421, - 398 - 385, - 376/ - 364 and - 363/ - 351, that de creased activity by similar to 2-fold each. Combined mutation of the region s - 434/ - 421, - 398/ - 385 and - 376/ - 364 decreased activity by 5-fold in thyrotropic cells and not at all in gonadotropic cells. Cotransfection w ith Ptx1 in CV-1 cells resulted in a strong stimulation of alpha-subunit pr omoter activity, that was significantly diminished with mutation of the - 3 98/ - 385 region that disrupts the Ptx1 binding site, suggesting that this factor may play a role in thyrotrope-specific activation. This analysis pro vides basic information important to identify common and unique factors con tributing to the cell-specific expression of the alpha-subunit gene. (C) 19 98 Elsevier Science Ireland Ltd. All rights reserved.