Novel Splicing of Immune System Thyroid Stimulating Hormone β-Subunit—Genetic Regulation and Biological Importance

Thyroid stimulating hormone (TSH), a glycoprotein hormone produced by the anterior pituitary, controls the production of thyroxine (T(4)) and triiodothyronine (T(3)) in the thyroid. TSH is also known to be produced by the cells of the immune system; however, the physiological importance of that to the organism is unclear. We identified an alternatively-spliced form of TSHβ that is present in both humans and mice. The TSHβ splice variant (TSHβv), although produced at low levels by the pituitary, is the primary form made by hematopoietic cells in the bone marrow, and by peripheral leukocytes. Recent studies have linked TSHβv functionally to a number of health-related conditions, including enhanced host responses to infection and protection against osteoporosis. However, TSHβv also has been associated with autoimmune thyroiditis in humans. Yet to be identified is the process by which the TSHβv isoform is produced. Here, a set of genetic steps is laid out through which human TSHβv is generated using splicing events that result in a novel transcript in which exon 2 is deleted, exon 3 is retained, and the 3′ end of intron 2 codes for a signal peptide of the TSHβv polypeptide.