Stimulation of thyroidal and extrathyroidal thyrotropin receptors

Abstract

TSH receptor plays a pivotal role in the regulation of thyroid function and is intimately involved in the pathogenesis of common thyroid disorders. A lack of specificity and absence of down regulation upon stimulation renders the human TSH receptor susceptible to exogenous overstimulation, which forms the basis of hyperthyroidism in TSHoma, Graves' disease and gestational thyrotoxicosis. Further, TSH receptor activation in the absence of exogenous stimulators due to the expression of endogenously active mutant receptors has recently been described, and may in part account for hyperthyroidism in autonomously functioning thyroid nodules. Signal bifurcating by coupling of TSH receptor to different G proteins may be a likely mechanism to explain the multitude of distinct effects caused by TSH receptor activation including mainly hormone production and growth promotion. Also, TSH receptor appears to mediate immunological stimulation, its activation by TSH R Ab inducing expression of adhesion molecules and HLA class II antigens on thyrocytes. Increasing evidence suggests that TSH receptor is not restricted to thyroid and may be expressed in extrathyroidal tissues with a potential role in the pathogenesis of Graves' orbitopathy.

TSH-induced gene expression involves regulation of self-renewal and differentiation-related genes in human bone marrow-derived mesenchymal stem cells

“…It is very well known that stimulation of TSHR by TSH results eventually in production of THs, T 3 and T 4 in thyroid cells (Toccafondi et al 1982, Szkudlinski et al 2002. However, we also know that TSHR can be expressed by extrathyroidal tissues or cells (Haraguchi et al 1996, Hoermann 1996, Dutton et al 1997, Bell et al 2000, Agretti et al 2002, Tsai et al 2004, Ellerhorst et al 2006. For example, kidney cells were shown to express a functional TSHR that transmitted signals through cAMP (Sellitti et al 2000).…”

“…Stimulation of the TSHR via TSH on thyroid cells leads to production of the thyroid hormones (THs), tri-iodothyronine (T 3 ) and thyroxine (T 4 ) (Toccafondi et al 1982). The TSHR expression by other tissue cells has also been reported (Haraguchi et al 1996, Hoermann 1996, Dutton et al 1997, Bell et al 2000, Agretti et al 2002, Tsai et al 2004, Ellerhorst et al 2006. However, exact function of its expression in extrathyroidal tissues has not been clarified.…”