Cloning and sequencing of a 1.3 kb variant of human thyrotropin receptor mRNA lacking the transmembrane domain

We amplified human thyroidal cDNA using oligonucleotide primers designed to reveal putative human thyrotropin receptor (hTSHR) mRNA variants encoding the extracellular, ligand-binding domain but lacking the transmembrane domain. Whereas the major 4.3 kb hTSHR mRNA species was not amplified to detectable levels, several shorter products were detected. A strongly amplified 1 kb product was cloned and sequenced. It contained coding sequences at the 5′ end which were colinear with exons 1-8 of the hTSHR gene, encoding most of the extracellular domain. This was followed at the 3′ end by additional coding and noncoding information not present in the 4.3 kb transcript. A probe specific for the 5′ end recognized polyadenylated thyroidal transcripts of 4.3, 1.7, and 1.3 kb, indicating the presence of several hTSHR mRNA variants. A probe specific for the 3′ end recognized only the 1.3 kb transcript. The level of the 1.3 kb variant (hTSHR-v1.3 mRNA) was about half that of the 4.3 kb hTSHR mRNA and twice that of the 1.7 kb variant. The presence of a thyroidal mRNA encoding both the signal peptide and ligand-binding region of the hTSHR, but not the seven transmembrane helices, provides the potential to produce soluble receptors which could play important roles in thyroid physiology and/or autoimmune thyroid disease.