The structure of the thyroid stimulating hormone receptor (TSHR) has attracted an unusual amount of discussion. Different authors have described a wide variety of receptor forms, with molecular masses varying from 90 to 500kDa, and comprising one to three subunits (reviewed in 1). A lack of precise structural information prevented the use of specific probes to clone the receptor. Two approaches to the problem were adopted. In one, the luteinizing hormone/chorionic gonadotrophin (LH/CG) receptor cDNA was initially cloned (2) and allowed the description of a novel family of G-protein-coupled receptors. This receptor was used as a probe in a crosshybridization experiment to clone the TSHR (3). The second approach involved the use of low-specificity PCR with probes derived from more distant G-protein-coupled receptors (4, 5).

The discovery of the homology of the TSHR with other G-protein-coupled receptors at the mRNA level led to the conclusion that the mature receptor was also a single subunit protein, but different molecular masses between 90 and 210 kDa were nevertheless proposed by different authors. This was mainly the result of a lack of adequate immunological tools with which to immunopurify the receptor before studying its structure. Because of the high hydrophobicity of the receptor and its tendency to aggregate with contaminating proteins, aberrant migration of receptor may have occurred on western blots. Another reason for the discrepant observations was the low concentration of the receptor in human thyroid glands, which has prompted most authors to study non-physiological systems, eg heterologous transfected cells. Cloning of the TSHR cDNA has allowed the structure of the protein to be deduced, with a calculated molecular mass of 85kDa that is highly homologous to the LH and follicle-stimulating hormone (FSH) receptors. All three receptors strikingly display the same division into regions according to their respective homology (6). The most homologous domain is the seven transmembrane domain (75% homology). Highly divergent regions within the extra-or intracellular domains can be demonstrated, however, and may be involved in more specific functions for each receptor. Contrasting with this high homology at the mRNA level, the mature structure of TSH and gonadotropin