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 subunit in pregnancy and in patients with trophoblastic diseases. To elucidate the differences in thyrotropic activity of hCG molecules, we examined cAMP accumulation and TSH receptor binding of intact hCG, hLH, and a recombinant hCG that lacked the C-terminal extension on the beta-subunit, hCG (alpha wt/beta delta T), using Chinese hamster ovary (CHO) cells transfected with hTSH receptors. hLH, which shares 85% sequence identity with the hCG-beta molecule except for the C-terminal amino acid residue extension of the hCG-beta subunit, bound to the TSH receptor and stimulated adenylate cyclase about 10 times more potently than hCG on a molar basis. This was consistent with the result that cAMP stimulation by mutant hCG (alpha wt/beta delta T) 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 demonstrate 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 beta-subunit occurs in the mixture of heterogeneous hCG molecular forms of pregnancy and trophoblastic diseases and may contribute to the hyperthyroidism in patients with hydatidiform mole, choriocarcinoma, and hyperemesis gravidarum.
Yoshimura
M
M
Endocrinology Research Laboratory, West Los Angeles Veterans Affairs Medical Center, California 90073.
Hershman
J M
JM
Pang
X P
XP
Berg
L
L
Pekary
A E
AE
D000704:Analysis of Variance; D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology; D016466:CHO Cells; D006063:Chorionic Gonadotropin / Q000502:physiology*; D018997:Chorionic Gonadotropin, beta Subunit, Human; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007455:Iodine / Q000378:metabolism; D007986:Luteinizing Hormone / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology; D051381:Rats; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology; D014162:Transfection
D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins; D007986:Luteinizing Hormone; D013972:Thyrotropin; D007455:Iodine; D000242:Cyclic AMP; D013936:Thymidine