Presence of thyrotropin receptor in hepatocytes: not a case of illegitimate transcription

Abstract

The function of thyrotropin (TSH) in the thyroid gland is mediated by thyrotropin receptor (TSHR). In addition to the thyroid, TSHR expression has been described in some non-thyroidal tissues, although it is uncertain whether TSHR is present in hepatocytes. One study has reported hepatic expression of TSHR mRNA, but this was considered to be because of illegitimate transcription, and there has not been a study investigating its protein expression and function in hepatocytes. Here, we examined the expression of TSHR in human and rat liver tissues, as well as human normal hepatocyte cell line L-02. Our results demonstrated that hepatic TSHR mRNA could be detected and had the same sequence as that of thyroid-derived mRNA. TSHR protein was also expressed and mainly located in the hepatocyte cell membrane. Moreover, bovine TSH and immunoglobulin from sera of patients with Graves’ disease stimulated cAMP production in these cells. Taken together, these data show that TSHR is present and functional in hepatocytes, and this expression is not a case of illegitimate transcription. Given the pivotal role of the liver in body metabolism and many human diseases, our findings provide important implications for a potentially novel physiopathological role of TSH via acting on the TSHR in hepatocytes besides its classical role in regulating the thyroid function.

A novel role for thyroid-stimulating hormone: Up-regulation of hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase expression through the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-responsive element binding protei

“…10 In the present study, by showing its coupling to the intracellular cAMP system and the expression of HMGCR, we established the functionality of this receptor in liver cells. This was unequivocally proven by the abolishment of the effects of TSH in cells treated with specific TSHR monoclonal antibodies or lentiviral TSHR siRNA to silence the expression of TSHR.…”

“…We previously demonstrated that TSHR expressed in liver cells, including human liver cells. 10 Here, we took further steps to examine and demonstrate a functional coupling of the TSHR to the cAMP system in the cells. Treatment with TSH significantly stimulated cAMP production in liver cells over the control ( Fig.…”

“…8,9 We recently demonstrated that TSHR was expressed in hepatocytes and that stimulation of cultured liver cells with TSH increased the production of cAMP. 10 These results suggested that the TSHR might play an important role in the regulation of liver function.…”

Lipid Profile in Type 2 Diabetes Mellitus with and Without Subclinical Hypothyroidism

“…The reported mechanisms for the development of hypercholesterolemia and an increase in low density lipoproteins in hypothyroidism include decreased fractional clearance of LDL by a reduced number and reduced activity of LDL receptors in the liver (4,13) . In vivo and in vitro studies of Wei Zhang et al (16) showed the presence of TSH receptor on liver cells. TSH itself upregulates the expression of HMG-COA -reductase by acting on a TSH receptor in hepatocyte membrane and therefore promotes cholesterol synthesis in liver (17) .…”

Decreased fasting blood glucose is associated with impaired hepatic glucose production in thyroid-stimulating hormone receptor knockout mice

“…Recently, multiple studies have found that extrathyroidic tissues express TSHR [11]. Our previous studies [12,13] demonstrated that functional TSHR was expressed samples were collected. The liver, heart and kidney were weighed, and the liver was divided into three parts.…”