ACTIVATION OF THE THYROTROPIN (TSH) RECEPTOR BY HUMAN CHORIONIC-GONADOTROPIN AND LUTEINIZING-HORMONE IN CHINESE-HAMSTER OVARY CELLS EXPRESSING FUNCTIONAL HUMAN TSH RECEPTORS

It is well known that peptide heterogeneity exists in the hCG-beta sub unit in pregnancy and in patients with trophoblastic diseases. To eluc idate the differences in thyrotropic activity of hCG molecules, we exa mined cAMP accumulation and TSH receptor binding of intact hCG, hLH, a nd a recombinant hCG that lacked the C-terminal extension on the beta- subunit, hCG (alphawt/betaDELTAT), using Chinese hamster ovary (CHO) c ells transfected with hTSH receptors. hLH, which shares 85% sequence i dentity with the hCG-beta molecule except for the C-terminal amino aci d residue extension of the hCG-beta subunit, bound to the TSH receptor and stimulated adenylate cyclase about 10 times more potently than hC G on a molar basis. This was consistent with the result that cAMP stim ulation by mutant hCG (alphawt/betaDELTAT) was greater than intact hCG . hLH also increased iodide uptake and thymidine incorporation in FRTL -5 rat thyroid cells more potently than intact hCG. These results demo nstrate that hLH is a more potent TSH than hCG and that the C-terminal extension of the hCG beta-subunit can interfere with hCG interaction with the hTSH receptor. hCG lacking the C-terminal extension of the be ta-subunit occurs in the mixture of heterogeneous hCG molecular forms of pregnancy and trophoblastic diseases and may contribute to the hype rthyroidism in patients with hydatidiform mole, choriocarcinoma, and h yperemesis gravidarum.