A novel thyroid stimulating hormone β-subunit isoform in human pituitary, peripheral blood leukocytes, and thyroid

Abstract

Thyroid stimulating hormone (TSH) is produced by the anterior pituitary and is used to regulate thyroid hormone output, which in turn controls metabolic activity. Currently, the pituitary is believed to be the only source of TSH used by the thyroid. Recent studies in mice from our laboratory have identified a TSHβ isoform that is expressed in the pituitary, in peripheral blood leukocytes (PBL), and in the thyroid. To determine whether a human TSHβ splice variant exists that is analogous to the mouse TSHβ splice variant, and whether the pattern of expression of the splice variant is similar to that observed in mice, PCR amplification of RNAs from pituitary, thyroid, PBL, and bone marrow was done by reverse-transcriptase PCR and quantitative realtime PCR. Human pituitary expressed a TSHβ isoform that is analogous to the mouse TSHβ splice variant, consisting of a 27 nucleotide portion of intron 2 and all of exon 3, coding for 71.2% of the native human TSHβ polypeptide. Of particular interest, the TSHβ splice variant was expressed at significantly higher levels than the native form or TSHβ in PBL and the thyroid. The TSHα gene also was expressed in the pituitary, thyroid, and PBL, but not the BM, suggesting that the TSHβ polypeptide in the thyroid and PBL may exist as a dimer with TSHα. These findings identify an unknown splice variant of human TSHβ. They also have implications for immune–endocrine interactions in the thyroid and for understanding autoimmune thyroid disease from a new perspective.