[Mechanism of regulation of TSH--biosynthesis and secretion]

The pituitary glycoprotein hormone, TSH, is synthesized and secreted by thyrotrophs in the anterior pituitary. Similarly to other pituitary glycoproteins, LH and FSH, it consists of two non-covalent subunits, alpha and beta. The alpha-subunit is common to all three hormones, while the beta-subunit is unique for each hormone. Both subunits are synthesized as separate peptides from distinct mRNA. T3 is the most important negative regulator of the TSH gene. The T3-T3 receptor complex binds to the specific promoter region, T3 response element (TRE), of its target genes and regulates the transcriptional activities. Although TREs have been studied in many genes, the TSH beta-TRE has not yet been fully identified. The mechanism how T3 suppresses TSH beta gene remains undetermined. Another important TSH gene regulator, TRH, is considered to stimulate the transcriptional activity by binding to the different promoter region of TSH beta gene. The interaction between TRH-response element and Pit-1/GHF-1, the pituitary specific factor, -response element is interesting. TRH affects TSH glycosylation, which is important to the biological activity. TSH in central hypothyroid patients is known to have a lower ratio of biological per immunological activity. Recently, in cases with congenital isolated TSH deficiency, a point mutation has been identified in the CAGY region of TSH beta gene, which is critical for dimer formation between alpha- and TSH beta-subunits.