Organization and nucleotide sequence of the mouse alpha-subunit gene of the pituitary glycoprotein hormones.

We have isolated and determined the nucleotide sequence of the mouse alpha-subunit gene of the pituitary glycoprotein hormones. No detectable rearrangements were observed from the cloned gene when compared with total genomic DNA. The gene is approximately 13.5 kb in size and consists of 4 exons and 3 introns. The 5' untranslated region is encoded by exon 1 and 14 bp of exon 2. A large first intron of about 10 kb interrupts the 5' untranslated region. The coding region is present in exons 2, 3, and 4, while the 3' untranslated region is contained entirely within exon 4. A number of mouse B1 and B2 repeats are present in the 5'-flanking region, the first and third introns, as well as in the 3'-flanking region. In contrast to the mouse beta-subunit gene of thyrotropin, primer extension analysis revealed that the alpha-subunit gene has a single transcriptional start site and that the primary transcript does not exhibit alternative exon splicing. The transcriptional start site is identical in both mouse pituitaries and in TtT97 thyrotropic tumors and is responsive to thyroidal status. The 5'-flanking region contains a sequence that is homologous to a single copy of the duplicated 18-bp cyclic AMP-responsive element of the human alpha-subunit gene. Sequences homologous to putative thyroid-responsive and estrogen responsive elements are present in the 5'-flanking region and may be important in the multihormonal regulation of the alpha-subunit gene in throtrophs and gonadotrophs, respectively.