Bone marrow cells produce a novel TSH beta splice variant that is upregulated in the thyroid following systemic virus infection

Although cells of the immune system can produce thyroid-stimulating hormone (TSH), the significance of that remains unclear. Using 5' rapid amplification of cDNA ends (RACE), we show that mouse bone marrow (BM) cells produce a novel in-frame TSH beta splice variant generated from a portion of intron 4 with all of the coding region of exon 5, but none of exon 4. The TSH beta splice variant gene was expressed at low levels in the pituitary, but at high levels in the BM and the thyroid, and the protein was secreted from transfected Chinese hamster ovary (CHO) cells. Immunoprecipitation identified an 8 kDa product in lysates of CHO cells transfected with the novel TSH beta construct, and a 17 kDa product in lysates of CHO cells transfected with the native TSH beta construct. The splice variant TSH beta protein elicited a cAMP response from FRTL-5 thyroid follicular cells and a mouse alveolar macrophage (AM) cell line. Expression of the TSH beta splice variant, but not the native form of TSH beta, was significantly upregulated in the thyroid during systemic virus infection. These studies characterize the first functional splice variant of TSH beta, which may contribute to the metabolic regulation during immunological stress, and may offer a new perspective for understanding autoimmune thyroiditis.