Somatic and germline mutations of the TSH receptor gene in thyroid diseases

Journal Article · Fri Sep 01 04:00:00 EDT 1995 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.80.9.2577· OSTI ID:430222

Van Sande, J; Parma, J; Tonacchera, M ^[1]

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1. and others

Under physiological circumstances, thyrotropin (TSH) is the primary hormone that controls thyroid function and growth. TSH acts by binding to its receptor at the basolateral membrane of thyroid follicular cells. The TSH receptor is a member of the large family of G protein-coupled receptors, which share a similar structural pattern: seven transmembrane segments connected by three extra and three intracellular loops. Together with the receptors for other glycoprotein hormones LH/CG and FSH, the TSH receptor has a long aminoterminal domain that has been shown to encode the specificity for hormone recognition and binding. The G protein-coupled receptors share a common mode of intracellular signalling: They control the on/off state of a variety of trimeric G proteins (G{alpha}{beta}{gamma}) by stimulating the exchange of GDP for GTP on the {alpha} subunit (G{alpha}). The result is that G{alpha} or G{beta}{gamma}, after dissociation of the trimer, will interact with downstream effectors of the receptor. In the case of the TSH receptor, the main G protein involved is Gs, which activates adenylyl cyclase via Gs{alpha}. In some species, including man, the TSH receptor is also capable of activating phospholipase C (via Gq), thus stimulating the production of diacylglycerol and inositolphosphate (IP{sub 3}). However, higher concentrations of TSH are required to activate phospholipase C, compared with adenylyl cyclase. As a consequence, the main second messenger of TSH effects on the human thyroid is cyclic AMP. The present review will summarize recent findings identifying mutations of the TSH receptor gene as a cause for thyroid diseases. 59 refs., 4 figs.

• OSTI ID: 430222
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 9 Vol. 80; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ENDOCRINE DISEASES
GENE MUTATIONS
GENES
RECEPTORS
SOMATIC MUTATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS
THYROID
TSH