The TSH receptor and its role in thyroid disease

Authors
Citation
P. Kopp, The TSH receptor and its role in thyroid disease, CELL MOL L, 58(9), 2001, pp. 1301-1322
Citations number
224
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELLULAR AND MOLECULAR LIFE SCIENCES
ISSN journal
1420-682X → ACNP
Volume
58
Issue
9
Year of publication
2001
Pages
1301 - 1322
Database
ISI
SICI code
1420-682X(200108)58:9<1301:TTRAIR>2.0.ZU;2-D
Abstract
The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiolog y and disease. TSH, acting through the TSH receptor, is the major stimulato r of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the target of stimulating antibodies that cause hypert hyroidism. Although still a topic of debate, the TSH receptor has been impl icated in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor are involved in the development of hypothyroidism in a subset of patients with autoimmun e hypothyroidism. Transplacental passage of stimulating or blocking TSH rec eptor antibodies from a mother with autoimmune thyroid disease may result i n transient hyper- or hypothyroidism in early infancy. During pregnancy, th e placental hormone human choriogonadotropin (hCG) can cause gestational hy perthyroidism through cross-reaction with the TSH receptor. Gestational hyp erthyroidism may also be involved in the pathogenesis of hyperemesis gravid arum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the ger mline give rise to nonautoimmune familial hyperthyroidism or sporadic conge nital hyperthyroidism. These gain-of-function mutations are dominant, and o ne mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor alleles lead to variable degrees of resista nce to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropin emia to overt hypothyroidism with thyroid hypoplasia.