Renal expression of two 'thyroid-specific' genes: Thyrotropin receptor andthyroglobulin

Numerous renal abnormalities accompany thyroid disease, most of which have been ascribed to the effects of thyroid hormone on renal metabolism. In the present report, we investigate the renal expression of the nominally thyro id-specific proteins, thyroid-stimulating hormone (TSH) receptor (TSHR) and thyroglobulin (Tg), as potential links between renal and thyroid function. The expression of TSHR has been identified in several extrathyroidal tissu es, but its presence in the kidney remains controversial. We have used reve rse-transcriptase polymerase chain reaction and DNA sequencing to demonstra te the presence of TSHR transcript in human and mouse kidney, in a primary culture of human kidney, and in a green monkey kidney epithelioid cell line . Furthermore, human kidney cells responded to TSH with a 2.5-fold increase in intracellular cyclic adenosine monophosphate, suggesting the presence o f functional TSHR protein. Comparison of renal expression of TSHR in a bovi ne growth hormone transgenic mouse model of progressive glomerulosclerosis with control mice suggested increased TSHR transcript in the renal cortex o f transgenic animals. TSHR transcript was also detected in mouse mesangial cells in vitro which responded to TSH with significant increases in the for mation of three-dimensional hillhocks. Polymerase chain reaction also confi rmed the presence of Tg transcript in human and mouse kidneys and in mouse mesangial cells, but no effect of either TSH or cyclic adenosine monophosph ate on Tg transcript levels could be discerned. Immunofluorescent staining with a monoclonal anti-Tg antibody identified positive staining in the cyto plasm of mesangial cells. These data suggest that the kidney is capable of expressing the thyroid-specific genes, TSHR and Tg, which could conceivably mediate effects of thyroid disease in the kidney. Copyright (C) 2000 S. Ka rger AG, Basel.