Isolation and characterization of the human thyrotropin beta-subunit gene. Differences in gene structure and promoter function from murine species.

The human thyrotropin beta-subunit gene was isolated and characterized from two genomic libraries and found to contain three exons separated by two introns of 3.9 and 0.45 kilobase pairs. Exons 2 and 3 in the mouse thyrotropin beta-subunit gene are not found in humans due to a lack of consensus sequences important in exon splicing. Moreover, using primer extension, RNA sequencing, and S1 nuclease analysis, we determined, in a thyrotropin-producing pituitary adenoma, that exon 1 in humans contains only one transcriptional start site and is 37 base pairs in length. This is unlike both the rat and mouse thyrotropin beta-subunit genes which contain two transcriptional start sites. Changes in the genomic structure of the more 5' "TATA box" and surrounding "CAAT box" might explain why the more 5' start site in humans is apparently not utilized. Moreover, the first exon in humans is longer than the corresponding exon in murine species presumably due to a 9-base pair insertion between the TATA box and transcriptional start site (37 versus 27 nucleotides). Thus, while alternative exon splicing and differential start site utilization in response to thyroid hormone may be important in the regulation of murine thyrotropin beta-subunit genes, they are not found in man.