The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin

Two glycoprotein hormone subunits, glycoprotein hormone subunit α (GPA) 2 and glycoprotein hormone subunit β (GPB) 5, have recently been discovered. When expressed as recombinant proteins, they heterodimerize to form a novel thyrotrophic hormone, thyrostimulin. Recently, we have shown that GPA2 is expressed in both human pancreas and anterior pituitary. To explore the transcriptional regulation of GPA2, we identified from human pancreas full length RNA, the transcription start site (TSS) of the human GPA2 gene. A potential binding site for the LIM homeodomain transcription factor isl-1, which is closely associated with endocrine organs, was found at - 2368 to - 2363 bp upstream from TSS. The exogenously expressed isl-1 dose-dependently increased the GPA2 promoter activity up to two-fold in the AtT20 mouse corticotroph cell line. In chromatin immunoprecipitation assays we show the binding of isl-1 molecule to the predicted site. The reporter assay also showed that GPA2 transcription is unaffected by tri-iodothyronine or thyroid hormone receptor β1 (TRβ1), suggesting that the regulation of GPA2 might be different from the regulations of GSUα or TSHβ, known as hypothalamus-pituitary-thyroid (HPT) axis. This study illustrated that human GPA2 is positively regulated by isl-1, suggesting that this protein associates with endocrine systems including the pituitary and pancreas.