This article describes the structure of human thyroid-stimulating hormone (TSH) gene and the regulation of its expression. TSH is a heterodimer composed of common alpha subunit and unique beta subunit encoded by genes located on different chromosomes. It is known that the expression of these subunit genes is regulated in different mechanism by several extracellular factors. The DNA sequencing data of the gene demonstrated that these genes were regulated by interaction of several potential regulatory elements with transcription factors. This transcriptional regulation was analyzed by transient expression of chimeric gene fragments and DNA-protein binding assay, in vitro. To identify the essential DNA regulatory elements of the human TSH beta gene in vivo, we introduced 1.1 kbp of the 5' flanking region of the human TSH beta gene-simian virus 40 T-antigen (SVT) fusion gene into the mouse. This region could direct pituitary-specific expression of SVT and tumorigenesis in transgenic mice.